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1. Intake Estimation of Phytochemicals in a French Well-Balanced Diet

Author: Marie-Josèphe Amiot, Christian Latgé, Laurence Plumey, Sylvie Raynal, Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Nutrition CO&CO, Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Antioxidant, Mediterranean diet, 030309 nutrition & dietetics, medicine.medical_treatment, Phytochemicals, healthy diet, Diet, Mediterranean, Antioxidants, Anthocyanins, chemistry.chemical_compound, phytonutrients, 0302 clinical medicine, Hydroxybenzoates, TX341-641, Food science, Carotenoid, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, organosulfur, Nutrition and Dietetics, carotenoids, food and beverages, 3. Good health, Phytochemical, Dietary Reference Intake, France, Plants, Edible, Adult, 030209 endocrinology & metabolism, Biology, Article, 03 medical and health sciences, Caffeine, medicine, Humans, polyphenols, Flavonoids, Sulfur Compounds, Nutrition. Foods and food supply, fungi, dietary recommendations, Diet, Human nutrition, chemistry, Polyphenol, Anthocyanin, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Tannins, Food Science
Abstract: International audience; Phytochemicals contribute to the health benefits of plant-rich diets, notably through their antioxidant and anti-inflammatory effects. However, recommended daily amounts of the main dietary phytochemicals remain undetermined. We aimed to estimate the amounts of phytochemicals in a well-balanced diet. A modelled diet was created, containing dietary reference intakes for adults in France. Two one-week menus (summer and winter) were devised to reflect typical intakes of plant-based foods. Existing databases were used to estimate daily phytochemical content for seven phytochemical families: phenolic acids, flavonoids (except anthocyanins), anthocyanins, tannins, organosulfur compounds, carotenoids, and caffeine. The summer and winter menus provided 1607 and 1441 mg/day, respectively, of total polyphenols (phenolic acids, flavonoids, anthocyanins, and tannins), the difference being driven by reduced anthocyanin intake in winter. Phenolic acids, flavonoids (including anthocyanins), and tannins accounted for approximately 50%, 25%, and 25% of total polyphenols, respectively. Dietary carotenoid and organosulfur compound content was estimated to be approximately 17 and 70 mg/day, respectively, in both seasons. Finally, both menus provided approximately 110 mg/day of caffeine, exclusively from tea and coffee. Our work supports ongoing efforts to define phytochemical insufficiency states that may occur in individuals with unbalanced diets and related disease risk factors.
Published: 2021
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2. Dereplication of Natural Extracts Diluted in Glycerin: Physical Suppression of Glycerin by Centrifugal Partition Chromatography Combined with Presaturation of Solvent Signals in 13C-Nuclear Magnetic Resonance Spectroscopy

Author: Richard Roe, Stéphane Poigny, Jane Hubert, Yves Brunel, Jean-Hugues Renault, Jean-Marc Nuzillard, Marine Canton, Institut de Chimie Moléculaire de Reims - UMR 7312 (ICMR), Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), NatExplore, Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre, SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Glycerol, glycerin, Magnetic Resonance Spectroscopy, cosmetic industry, Centrifugal partition chromatography, Pharmaceutical Science, Fractionation, Chemical Fractionation, Complex Mixtures, 01 natural sciences, Article, Analytical Chemistry, lcsh:QD241-441, centrifugal partition chromatography, natural extract, lcsh:Organic chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Tandem Mass Spectrometry, Drug Discovery, Physical and Theoretical Chemistry, Solvent system, Biological Products, Chromatography, 010405 organic chemistry, Chemistry, Plant Extracts, Organic Chemistry, 13C nuclear magnetic resonance, Nuclear magnetic resonance spectroscopy, chemical profiling, 0104 chemical sciences, Dilution, Solvent, 010404 medicinal & biomolecular chemistry, Chemistry (miscellaneous), Solvents, Molecular Medicine, Sugars, [CHIM.CHEM]Chemical Sciences/Cheminformatics, Chromatography, Liquid
Abstract: For scientific, regulatory, and safety reasons, the chemical profile knowledge of natural extracts incorporated in commercial cosmetic formulations is of primary importance. Many extracts are produced or stabilized in glycerin, a practice which hampers their characterization. This article proposes a new methodology for the quick identification of metabolites present in natural extracts when diluted in glycerin. As an extension of a 13C nuclear magnetic resonance (NMR) based dereplication process, two complementary approaches are presented for the chemical profiling of natural extracts diluted in glycerin: A physical suppression by centrifugal partition chromatography (CPC) with the appropriate biphasic solvent system EtOAc/CH3CN/water 3:3:4 (v/v/v) for the crude extract fractionation, and a spectroscopic suppression by presaturation of 13C-NMR signals of glycerin applied to glycerin containing fractions. This innovative workflow was applied to a model mixture containing 23 natural metabolites. Dereplication by 13C-NMR was applied either on the dry model mixture or after dilution at 5% in glycerin, for comparison, resulting in the detection of 20 out of 23 compounds in the two model mixtures. Subsequently, a natural extract of Cedrus atlantica diluted in glycerin was characterized and resulted in the identification of 12 metabolites. The first annotations by 13C-NMR were confirmed by two-dimensional NMR and completed by LC-MS analyses for the annotation of five additional minor compounds. These results demonstrate that the application of physical suppression by CPC and presaturation of 13C-NMR solvent signals highly facilitates the quick chemical profiling of natural extracts diluted in glycerin.
Published: 2020
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3. Taxonomically informed metabolite annotation and data organization in natural products research

Author: B David, Jonathan Bisson, Miwa Dounoue-Kubo, Adriano Rutz, Joël Boustie, Simon Ollivier, D Olivier, LM Quiros Guerrero, J-L Wolfender, PM Allard, A Gaudry, Université de Lausanne (UNIL), Université de Genève (UNIGE), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), University of Chicago, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Université de Lausanne = University of Lausanne (UNIL), Université de Genève = University of Geneva (UNIGE), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: chemistry.chemical_compound, Annotation, chemistry, Metabolite, [CHIM]Chemical Sciences, Computational biology, Biology, Natural (archaeology), ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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4. Stabilization of microtubules restores barrier function after cytokine-induced defects in reconstructed human epidermis

Author: Valérie Pendaries, Nicolas Lecland, Cécile Viodé, Andreas Merdes, Christiane Bierkamp, Carle Paul, Daniel Redoules, Michel Simon, Chiung-Yueh Hsu, Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Hôpital Larrey [Toulouse], and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, Keratinocytes, Intercellular junctions, Paclitaxel, [SDV]Life Sciences [q-bio], Cell Culture Techniques, Human skin, Dermatology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Lamellar granule, Filaggrin Proteins, Biochemistry, Microtubules, Dermatitis, Atopic, 03 medical and health sciences, chemistry.chemical_compound, Stabilization of microtubules, Microtubule, Cell cortex, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Humans, Molecular Biology, Barrier function, Cells, Cultured, MESH: Cell Culture Techniques Cells, Cultured Cytokines / metabolism Dermatitis, Atopic / drug therapy Dermatitis, Atopic / pathology Epidermal Cells Epidermis / drug effects* Epidermis / pathology Epothilones / pharmacology Epothilones / therapeutic use Humans Keratinocytes / cytology Keratinocytes / drug effects* Keratinocytes / pathology Microtubules / drug effects* Microtubules / pathology Paclitaxel / pharmacology Paclitaxel / therapeutic use Tubulin Modulators / pharmacology* Tubulin Modulators / therapeutic use Water Loss, Insensible / drug effects, Epidermis (botany), Chemistry, Keratinocyte differentiation, Lamellar bodies, Water Loss, Insensible, Tubulin Modulators, Barrier recovery, Cell biology, Nocodazole, 030104 developmental biology, Epidermal Cells, Epothilones, Loricrin, Cytokines, Epidermis
Abstract: International audience; Background: A variety of human skin disorders is characterized by defects in the epidermal barrier, leading to dehydration, itchiness, and rashes. Previously published literature suggests that microtubule stabilization at the cortex of differentiating keratinocytes is necessary for the formation of the epidermal barrier. Objectives: We tested whether stabilization of microtubules with paclitaxel or epothilone B can repair barrier defects that were experimentally induced in three-dimensional culture models of epidermis. Methods: We established two models of defective epidermis in vitro, using three-dimensional cultures of primary human keratinocytes on filter supports: immature reconstructed human epidermis (RHE), and RHE that was compromised by treatment with inflammatory cytokines, the latter mimicking defects seen in atopic dermatitis. Results: Both paclitaxel and epothilone B promoted keratinocyte differentiation, accumulation of junctional proteins at the cell cortex, and the early appearance of lamellar bodies in immature RHE, whereas destabilization of microtubules by nocodazole had the reverse effect. Moreover, stabilization of microtubules rescued the barrier after cytokine treatment. The rescued barrier function correlated with the restoration of filaggrin and loricrin protein levels, the cortical accumulation of junctional proteins (E-cadherin, β-catenin, and claudin-1), and with the secretion of lamellar bodies. Conclusions: Our data suggest that the microtubule network is important for the formation of the epidermis, and that stabilization of microtubules promotes barrier formation. Microtubule stabilization may support regeneration of damaged skin, by restoring or improving the barrier.
Published: 2018
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5. The use of suction blisters to measure sunscreen protection against UVR- induced DNA damage

Author: Emmanuel Questel, Eléonore Gravier, Gwendal Josse, Thierry Douki, Jimmy Le Digabel, CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Res Ctr, Institut Curie, Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, 0301 basic medicine, Suction (medicine), Ultraviolet Rays, DNA damage, education, Biophysics, Pyrimidine dimer, medicine.disease_cause, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, Blister, 0302 clinical medicine, Tandem Mass Spectrometry, Healthy volunteers, medicine, Humans, Radiology, Nuclear Medicine and imaging, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, Skin, Radiation, integumentary system, Radiological and Ultrasound Technology, Chemistry, food and beverages, Blisters, Molecular biology, Suction blister, Staining, 030104 developmental biology, Pyrimidine Dimers, Female, medicine.symptom, Sun Protection Factor, Sunscreening Agents, Genotoxicity, DNA Damage
Abstract: The formation of DNA photoproducts caused by solar UVR exposure needs to be investigated in-vivo and in particular in order to assess sunscreens' level of protection against solar genotoxicity. The study's purposes were: i) to evaluate if the roof of suction blisters is an appropriate sampling method for measuring photoproducts, and ii) to measure in-vivo sunscreen protection against cyclobutane pyrimidine dimers. Skin areas on the interior forearms of eight healthy volunteers were exposed in-vivo to 2 MED of simulated solar radiation (SSR) and to 15 MED on a sunscreen protected area. After irradiation, six suction blisters were induced and the blister roofs were collected. Analysis of SSR-induced CPDs was performed by two independent methods: a chromatography coupled to mass spectroscopy (HPLC-MS/MS) approach and a 3D-imaging of CPD immunostaining by multiphoton microscopy on floating epidermal sheets. HPLC-MS/MS analyses showed that SSR-unexposed skin presented no CPD dimers, whereas 2 MED SSR-exposed skin showed a significant number of TT-CPD. The sunscreen covered skin exposed to 15 MED appeared highly protected from DNA damage, as the amount of CPD-dimers remained below the detection limit. The multiphoton-immunostaining analysis consistently showed that no CPD staining was observed on the non-SSR-exposed skin. A significant increase of CPD staining intensity and number of CPD-positive cells were observed on the 2 MED SSR-exposed skin. Sunscreen protected skin presented a very low staining intensity and the number of CPD-positive cells remained very close to non-SSR-exposed skin. This study showed that suction blister samples are very appropriate for measuring CPD dimers in-vivo, and that sunscreens provide high protection against UVR-induced DNA damage.
Published: 2018
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6. Editor’s Highlight: Fragrance Allergens Linalool and Limonene Allylic Hydroperoxides in Skin Allergy: Mechanisms of Action Focusing on Transcription Factor Nrf2

Author: Salen Kuresepi, Jean-Pierre Lepoittevin, Chloé Raffalli, Marc Pallardy, Saadia Kerdine-Römer, Elena Giménez-Arnau, Marie-Hélène Damiens, Elodie Clouet, Pierre-Jacques Ferret, Inflammation, Chimiokines et Immunopathologie [Châtenay-Malabry], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: 0301 basic medicine, cell surface thiol, Stereochemistry, Cell Survival, NF-E2-Related Factor 2, Acyclic Monoterpenes, Cell Culture Techniques, Toxicology, medicine.disease_cause, Monocytes, Nrf2, Cell Line, Terpene, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Allergic contact dermatitis, Autoxidation, Local lymph node assay, Activator (genetics), Glutathione, Hydrogen Peroxide, Allergens, medicine.disease, Perfume, 030104 developmental biology, chemistry, Biochemistry, Dermatitis, Allergic Contact, sensitizers, Monoterpenes, Signal transduction, allergic contact dermatitis, Oxidative stress, Limonene, terpenes, allylic hydroperoxides
Abstract: International audience; Allergic contact dermatitis is regarded as the most frequent expression of immunotoxicity in humans. Many odorant terpenes commonly used in fragrance compositions are considered as weak skin sensitizers, whereas some of their autoxidation products, allylic hydroperoxides, are classified as strong sensitizers according to the local lymph node assay. However, the mechanism of their effects on the immune system remains unclear. Since dendritic cells play a key role in allergic contact dermatitis, we studied their activation by the frequently used linalool (LINA) and limonene (LIMO), and their respective sensitizing allylic hydroperoxides (LINA-OOH, LIMO-OOH). The THP-1 cell-line was used as a surrogate for dendritic cells, the model currently employed in the validated h-CLAT in vitro test. Our data showed that allylic hydroperoxides behave differently. Both LINA-OOH and LIMO-OOH oxidized cell surface thiols 30 min after stimulation. However, the oxidative stress induced by LINA-OOH was stronger, with a higher decreased GSH/GSSG ratio and a stronger reactive species production. Moreover, LINA-OOH induced a stronger Nrf2 accumulation in correlation with nqo1 and ho-1 gene expression, 2 Nrf2 target genes. Regarding signaling pathways involved in these effects, P38 mitogen-activated protein kinase and P-ERK were activated in response to LINA-OOH but not with LIMO-OOH. CD54 and CD86 were induced 24-h postexposure. In contrast, LINA and LIMO did not modify THP-1 phenotype. This work underlies that autoxidation forming allylic hydroperoxide (ROOH) does not lead to equal chemical reactivity since LINA-OOH appears to be a stronger activator than LIMO-OOH, in regard to oxidative stress and Nrf2 pathway activation.
Published: 2018
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7. Chemical analysis and potential endocrine activities of aluminium coatings intended to be in contact with cosmetic water

Author: Pierre-Jacques Ferret, Elias Bou-Maroun, Sandrine Rakotomalala, Laurence Dahbi, Philippine Pierre, Marie-Christine Chagnon, Marie-Pierre Gomez-Berrada, Procédés Alimentaires et Microbiologiques [Dijon] ( PAM ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté ( UBFC ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre, Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: 0301 basic medicine, Agonist, medicine.drug_class, Non-intended added substances, Clinical Biochemistry, Endocrine activities, Pharmaceutical Science, Endocrine System, Reporter gene bioassay, Cosmetics, 010501 environmental sciences, 01 natural sciences, Gas Chromatography-Mass Spectrometry, Cell Line, Analytical Chemistry, 03 medical and health sciences, GC/HPLC–MS, Drug Discovery, Estrogenic potency, medicine, Humans, Endocrine system, Bioassay, Solid phase extraction, Spectroscopy, 0105 earth and related environmental sciences, High concentration, Chromatography, Chemistry, Water, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, In vitro, cosmetic aluminium coating, 030104 developmental biology, Biological Assay, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Gas chromatography–mass spectrometry, Water Pollutants, Chemical, Aluminum
Abstract: International audience; The objective of the work was to check the presence of Non-Intended Added Substances (NIAS) with hormonal activities in aluminium coatings extracts coded: AA, BBF, MC and RR, furnished by four different suppliers. Water samples were prepared at room temperature or at 40°C for three months to verify the storage effect on the coatings. Solid phase extraction was used to concentrate and to extract coating substances. Hormonal activities were checked in vitro using reporter gene bioassays. Except BBF, all extracts induced a weak but significant estrogenic agonist activity in the human cell line. Using an estrogenic antagonist (ICI-182, 780), the answer was demonstrated specific in the bioassay. RR was the only extract to induce a concentration dependent anti-androgenic response in the MDA-KB2 cell line. Analysis performed using GC-MS and HPLC-MS detected 12 substances in most of the extracts. 8 NIAS were present. Among them, 4 were identified with certainty: HMBT, BGA, DCU and BPA. Estrogenic potency was BPA>DCU>BGA>HMBT. HMBT was also anti-androgenic at high concentration. Combining chemical analysis and bioassays data, we demonstrated that in the RR and the RR40 extracts, the observed estrogenic response was mainly due to BPA, the anti-androgenic activity of RR could be due to a synergism between HMBT and BPA. For MC and AA, estrogenic responses appear to be due to the presence of DCU. Except BBF, storage conditions tended to increase estrogenic activities in all extracts. However, in term of risk assessment, activities observed were negligible. This work demonstrated that sensitive bioassays are pertinent tools in complement to chemical analysis to monitor and check the presence of NIAS with hormonal activity in coating extracts.
Published: 2017
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8. Identification of ageing biomarkers in human dermis biopsies by thermal analysis (DSC) combined with Fourier transform infrared spectroscopy (FTIR/ATR)

Author: P. Bianchi, Marie-Hélène Lacoste-Ferré, Florence Nadal-Wollbold, Patrick Bogdanowicz, Jany Dandurand, Valérie Samouillan, Rong Tang, Aurélie Villaret, Colette Lacabanne, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Laboratoires Pierre Fabre (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: 0301 basic medicine, Adult, Secondary structures of proteins, Protein Denaturation, Biopsy, Matériaux, Analytical chemistry, Hydration, Human skin, Dermatology, Absorption (skin), Human skin ageing, Vibration, [SPI.MAT]Engineering Sciences [physics]/Materials, Absorbance, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Differential scanning calorimetry, Dermis, Spectroscopy, Fourier Transform Infrared, medicine, Humans, Fourier transform infrared spectroscopy, Thermal analysis, Aged, integumentary system, Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, Middle Aged, Skin Aging, Collagen denaturation, 030104 developmental biology, medicine.anatomical_structure, Ageing, Sunlight, Collagen, Biomarkers, Biomedical engineering
Abstract: International audience; Background/purpose : The purpose of this clinical study was to identify suitable biomarkers for a better understanding of the molecular and organizational changes in human dermis during intrinsic and extrinsic ageing. Methods : Sun-exposed and non-exposed skin biopsies were collected from twenty-eight women devised in two groups (20-30 and ≥60 years old). The hydric organization and thermal transitions were determined by Differential Scanning Calorimetry (DSC). Fourier Transform Infrared spectroscopy (FTIR) was used to identify the absorption bands of the dermis and to quantify the different absorbance ratio. Results : The amounts of total, freezable and unfreezable water were determined. A significant increasing amount of freezable water is evidenced in sun-exposed area skin of aged group compared with young group (P=.0126). Another significant effect of extrinsic ageing (P=.0489) is the drastic decrease of fibrillary collagen, the main protein component of dermis. The only significant effect of intrinsic ageing (P=.0184) is an increase of the heat-stable fraction of collagens in dermis. Conclusion : DSC and FTIR are well-suited techniques to characterize human skin, giving accurate results with a high reproducibility. The combination of these techniques is useful for a better understanding of human skin modifications with intrinsic and extrinsic ageing.
Published: 2017
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9. Characterization of xenobiotic metabolizing enzymes of a reconstructed human epidermal model from adult hair follicles

Author: Daniel Bacqueville, Hélène Duplan, Emilien L. Jamin, Laure Duprat, Sandrine Bessou-Touya, Daniel Zalko, Elisabeth Perdu, Carine Jacques, Béatrice Guiraud, Département Pharmacologie, Service Pharmacologie Division 2 et Pharmacocinétique Cutané, Pierre Fabre Dermo-cosmétique, Centre de Recherche Pierre Fabre, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bacqueville, Daniel, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Keratinocytes, [SDV]Life Sciences [q-bio], Aldehyde dehydrogenase, Human skin, Toxicology, Outer root sheath, Ligands, human health, HSD17B10, Substrate Specificity, Cytochrome P-450 Enzyme System, Gene expression, Basic Helix-Loop-Helix Transcription Factors, Cells, Cultured, Glutathione Transferase, chemistry.chemical_classification, Cytochrome P-450 Enzyme Inducers, tissu cutané, biology, integumentary system, hair follicle, coat, épiderme, santé humaine, enzyme du métabolisme des xénobiotiques, Isoenzymes, cutaneous metabolism, medicine.anatomical_structure, Biochemistry, Enzyme Induction, dermatologie, Sulfotransferases, expression des gènes, reconstructed human epidermis, gene expression, functional activity, Xenobiotics, 03 medical and health sciences, medicine, Humans, Pharmacology, Metabolism, Hair follicle, Metabolic Detoxication, Phase II, Kinetics, 030104 developmental biology, Enzyme, chemistry, Receptors, Aryl Hydrocarbon, peau, biology.protein, Metabolic Detoxication, Phase I, cheveu
Abstract: In this study, a comprehensive characterization of xenobiotic metabolizing enzymes (XMEs) based on gene expression and enzyme functionality was made in a reconstructed skin epidermal model derived from the outer root sheath (ORS) of hair follicles (ORS-RHE). The ORS-RHE model XME gene profile was consistent with native human skin. Cytochromes P450 (CYPs) consistently reported to be detected in native human skin were also present at the gene level in the ORS-RHE model. The highest Phase I XME gene expression levels were observed for alcohol/aldehyde dehydrogenases and (carboxyl) esterases. The model was responsive to the CYP inducers, 3-methylcholanthrene (3-MC) and β-naphthoflavone (βNF) after topical and systemic applications, evident at the gene and enzyme activity level. Phase II XME levels were generally higher than those of Phase I XMEs, the highest levels were GSTs and transferases, including NAT1. The presence of functional CYPs, UGTs and SULTs was confirmed by incubating the models with 7-ethoxycoumarin, testosterone, benzo(a)pyrene and 3-MC, all of which were rapidly metabolized within 24h after topical application. The extent of metabolism was dependent on saturable and non-saturable metabolism by the XMEs and on the residence time within the model. In conclusion, the ORS-RHE model expresses a number of Phase I and II XMEs, some of which may be induced by AhR ligands. Functional XME activities were also demonstrated using systemic or topical application routes, supporting their use in cutaneous metabolism studies. Such a reproducible model will be of interest when evaluating the cutaneous metabolism and potential toxicity of innovative dermo-cosmetic ingredients.
Published: 2017
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10. Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors

Author: Etienne Decroly, Nils Marechal, Jean Cavarelli, V. Cura, Céline Faux, L. Bonnefond, Dominique Guianvarc'h, Frédéric Alby, Patrick Page, Paola B. Arimondo, Ludovic Halby, Jean-Claude Guillemot, Nathalie Troffer-Charlier, Don-Marc Franchini, Srikanth Kudithipudi, Clotilde Ferroud, Dany Pechalrieu, Wahiba Aouadi, Albert Jeltsch, Pharmacochimie de la Régulation Epigénétique du Cancer (ETaC), PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre, Universität Stuttgart [Stuttgart], Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie moléculaire, génie des procédés chimiques et énergétiques (CMGPCE), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), PIERRE FABRE-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, PRMT inhibitor, Methyltransferase, Chemical biology, DNA methyltransferase, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, chemical probes, Catalytic Domain, Histone methylation, Humans, histone methylation, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Binding site, DNA methylation, epigenetics, Articles, Methyltransferases, transition state analogues, Methylation, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, 030104 developmental biology, Biochemistry, chemistry, Peptides, General Agricultural and Biological Sciences, DNA
Abstract: DNA, RNA and histone methylation is implicated in various human diseases such as cancer or viral infections, playing a major role in cell process regulation, especially in modulation of gene expression. Here we developed a convergent synthetic pathway starting from a protected bromomethylcytosine derivative to synthesize transition state analogues of the DNA methyltransferases. This approach led to seven 5-methylcytosine-adenosine compounds that were, surprisingly, inactive against hDNMT1, hDNMT3Acat, TRDMT1 and other RNA human and viral methyltransferases. Interestingly, compound 4 and its derivative 2 showed an inhibitory activity against PRMT4 in the micromolar range. Crystal structures showed that compound 4 binds to the PRMT4 active site, displacing strongly the S -adenosyl- l -methionine cofactor, occupying its binding site, and interacting with the arginine substrate site through the cytosine moiety that probes the space filled by a substrate peptide methylation intermediate. Furthermore, the binding of the compounds induces important structural switches. These findings open new routes for the conception of new potent PRMT4 inhibitors based on the 5-methylcytosine-adenosine scaffold. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
Published: 2018
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11. Characterisation of B(a)P metabolites formed in an ex vivo pig skin model using three complementary analytical methods

Author: Carine Jacques, Emilien L. Jamin, Alain Mavon, Elisabeth Perdu, Laurent Debrauwer, Hélène Duplan, Daniel Zalko, Institut National de la Recherche Agronomique (INRA), Xénobiotiques, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Pharmacocinétique Cutanée (LABORATOIRE DE PHARMACOCINéTIQUE CUTANéE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Electrospray, Swine, [SDV]Life Sciences [q-bio], Metabolite, 010501 environmental sciences, Tandem mass spectrometry, Mass spectrometry, 01 natural sciences, Biochemistry, High-performance liquid chromatography, Analytical Chemistry, chemistry.chemical_compound, Glucuronic Acid, Tandem Mass Spectrometry, Benzo(a)pyrene, Animals, Ear, External, Chromatography, High Pressure Liquid, Skin, 0105 earth and related environmental sciences, Chromatography, Molecular Structure, Sulfates, 010401 analytical chemistry, Stereoisomerism, Glucuronic acid, 0104 chemical sciences, chemistry, Models, Animal, Female, Oxidation-Reduction, Ex vivo
Abstract: International audience; An original method was developed to separate, identify and quantify the different benzo(a)pyrene (B(a)P) metabolites formed through oxidative and conjugative pathways. All B(a)P metabolites were separated by an improved high-performance liquid chromatography method, then detected and quantified relatively by online radioactivity detection. At the same time, metabolite structures were characterised by tandem mass spectrometry using two complementary ionisation modes: electrospray ionisation in the negative mode and atmospheric pressure chemical ionisation in the positive mode. This method was successfully applied to the analysis of B(a)P metabolites, produced by incubation of B(a)P with the ex vivo pig ear skin model. These include glucuronic acid and sulphate conjugates of B(a)P-OHs and B(a)P-diols, as well as direct phase I metabolites: B(a)P-tetrol, B(a)P-diones, B(a)P-catechols, B(a)P-diols and B(a)P-OHs.
Published: 2010
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12. A Myrtus communis extract enriched in myrtucummulones and ursolic acid reduces resistance of Propionibacterium acnes biofilms to antibiotics used in acne vulgaris

Author: Christine Roques, Catherine Feuillolay, Sophie Pecastaings, Joelle Luc, Christel Fiorini-Puybaret, Céline Le Gac, Philippe Joulia, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Laboratoires Pierre Fabre (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), FONdation pour le DEveloppement de la REcherche PHARmaceutique- FONDEREPHAR (FRANCE), Laboratoire de Génie Chimique - LGC (Toulouse, France), Institut National Polytechnique de Toulouse - INPT (FRANCE), FONdation pour le DEveloppement de la REcherche PHARmaceutique - FONDEREPHAR (FRANCE), Laboratoire de Génie Chimique (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, and PIERRE FABRE-PIERRE FABRE
Subjects: 0301 basic medicine, medicine.drug_class, 030106 microbiology, Antibiotics, Erythromycin, Pharmaceutical Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Microbial Sensitivity Tests, Phloroglucinol, Microbiology, 03 medical and health sciences, Propionibacterium acnes, Drug Discovery, Acne Vulgaris, medicine, Génie chimique, Acne vulgaris, Génie des procédés, Pharmacology, Myrtus communis, biology, Chemistry, Plant Extracts, Biofilm, Clindamycin, biochemical phenomena, metabolism, and nutrition, Antimicrobial, biology.organism_classification, Microbiologie et Parasitologie, Myrtus, Triterpenes, Anti-Bacterial Agents, Complementary and alternative medicine, Biofilms, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Myrtle extract, Molecular Medicine, Bacteria, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.drug
Abstract: BackgroundRecent works present evidence of Propionibacterium acnes growing as a biofilm in cutaneous follicles. This formation of clusters is now considered as an explanation for the in vivo resistance of P. acnes to the main antimicrobials prescribed in acne vulgaris.PurposeOur objective was to explore this hypothesis and propose a new therapeutic approach focusing on anti-biofilm activity of Myrtacine® New Generation (Mediterranean Myrtle extract–Botanical Expertise P. Fabre) alone or combined with antibiotics.Methods/ResultsUsing in vitro models able to promote the growth of adhered bacteria, the loss of sensitivity of P. acnes biofilms (48 h) towards erythromycin and clindamycin was checked considering either sensitive or resistant strains. In the same time, the activity of Myrtacine® New Generation against biofilm formation and mature biofilm (48 h) was evaluated. Using a dynamic model of biofilm formation, we noted an inhibition of biofilm formation (addition of Myrtacine® New Generation at T 0) and a significant effect on mature biofilm (48 h) for 5 min of contact. This effect was also checked using the static model of biofilm formation for Myrtacine® New Generation concentrations ranging from 0.03% to 0.0001%. A significant, dose-dependent anti-biofilm effect was observed and notable even at a concentration lower than the active concentration on planktonic cells, i.e. 0.001%. Finally, the interest of the combination of Myrtacine® New Generation with antibiotics was explored. An enhanced efficacy was noted when erythromycin (1000 mg/l) or clindamycin (500 mg/l) was added to 0.001% Myrtacine®, leading to significant differences in comparison to each compound used alone.ConclusionThe efficiency of Myrtacine® New Generation on P. acnes biofilm alone or combined with antibiotics was demonstrated and can lead to consider it as a potent adjunctive product efficient during the antibiotic course for acne vulgaris treatment.
Published: 2015
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13. Acefylline activates filaggrin deimination by peptidylarginine deiminases in the upper epidermis

Author: Jean-Louis Vidaluc, Hélène Duplan, Sandrine Bessou-Touya, Hidenari Takahara, Guy Serre, Stephane Poigny, Sylvie Daunes-Marion, Marie-Florence Galliano, Marie-Claire Méchin, Michel Simon, Laura Cau, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, and Ibaraki University
Subjects: 0301 basic medicine, Keratinocytes, Models, Molecular, Hydrolases, Protein Conformation, MESH: Protein-Arginine Deiminases, Epidermal barrier, Filaggrin Proteins, Biochemistry, MESH: Dose-Response Relationship, Drug, MESH: Humans Hydrolases / metabolism, chemistry.chemical_compound, MESH: Structure-Activity Relationship, MESH: Protein Conformation, MESH: Theophylline / chemistry, MESH: Epidermis / enzymology, Intermediate Filament Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Keratinocytes / drug effects, Cells, Cultured, Skin, MESH: Enzyme Activators / administration & dosage, Citrullination, MESH: Administration, Cutaneous, medicine.anatomical_structure, MESH: Keratinocytes / enzymology, Post-translational modification, MESH: Intermediate Filament Proteins / metabolism, Filaggrin, MESH: Models, Molecular, MESH: Cells, Cultured, MESH: Enzyme Activation, MESH: Theophylline / administration & dosage, MESH: Theophylline / analogs & derivatives, MESH: Enzyme Activators / chemistry, Enzyme Activators, Dermatology, MESH: Theophylline / pharmacology, Administration, Cutaneous, Xanthine, Small Molecule Libraries, 03 medical and health sciences, Enzyme activator, Structure-Activity Relationship, MESH: Computer Simulation, Theophylline, MESH: Small Molecule Libraries, MESH: Enzyme Activators / pharmacology, Stratum corneum, medicine, Humans, Computer Simulation, Enhancer, Molecular Biology, MESH: Epidermal Cells Epidermis / drug effects, 030102 biochemistry & molecular biology, Epidermis (botany), Dose-Response Relationship, Drug, Activator (genetics), Enzyme Activation, 030104 developmental biology, chemistry, Epidermal Cells, MESH: Protein Processing, Post-Translational, Protein-Arginine Deiminases, Epidermis, MESH: Intermediate Filament Proteins / chemistry, Protein Processing, Post-Translational
Abstract: International audience; Background: Peptidylarginine deiminases (PADs) catalyze deimination (or citrullination), a calcium-dependent post-translational modification involved in several physiological processes and human diseases, such as rheumatoid arthritis and cancer. Deimination of filaggrin (FLG) by PAD1 and PAD3 during the last steps of keratinocyte differentiation is a crucial event for the epidermis function and homeostasis. This allows the complete degradation of FLG, leading to the production of free amino acids and their derivatives that are essential for epidermal photoprotection and moisturizing of the stratum corneum. Objective: To increase the flux of this catabolic pathway, we searched for activators of PADs. Methods: A large chemical library was screened first in silico and then by using an automated assay based on an indirect colorimetric measurement of recombinant human PAD activity. Potential activators were then confirmed using a recombinant human FLG as a substrate, and secondly after topical application at the surface of three-dimensional reconstructed human epidermis. Results: The data obtained after the library screening pointed to xanthine derivatives as potential PAD activators. Among seven xanthine derivatives tested at 50-300μM, caffeine, theobromine and acefylline proved to be the most potent enhancers of in vitro deimination of FLG by PAD1 and PAD3. After topical application of a gel formulation containing 3% acefylline at the surface of reconstructed epidermis, immunoblotting analysis showed an increase in the total amount of deiminated proteins, and confocal microscopy showed an enhanced deimination in the stratum corneum. This demonstrated the activation of PADs in living cells. Conclusion: As a PAD activator, acefylline will be useful to study the role of deimination and could be proposed to increase or correct the hydration of the cornified layers of the epidermis.
Published: 2015
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14. Cytisine-like alkaloids from Ormosia hosiei Hemsl.E.H. Wilson

Author: Isabelle Pouny, Sirong Yi, Muriel Batut, Laure Vendier, François Sautel, Bruno David, Georges Massiot, Paola B. Arimondo, Pharmacochimie de la Régulation Epigénétique du Cancer (ETaC), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-PIERRE FABRE, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Chongqing Institute of Medicinal Plant Cultivation, and China Academy of Chinese Medical Sciences
Subjects: Stereochemistry, Molecular Conformation, Plant Science, Horticulture, Ormosia hosiei, Receptors, Nicotinic, Crystallography, X-Ray, Biochemistry, Plant Roots, chemistry.chemical_compound, Cytisine, Alkaloids, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, Octane, biology, Molecular Structure, Plant Stems, Chemistry, Absolute configuration, Fabaceae, General Medicine, biology.organism_classification, Azocines, Nicotinic agonist, Alpha-4 beta-2 nicotinic receptor, Quinolizines
Abstract: International audience; Four alkaloids named hosieines A–D were isolated from the root and stem of Ormosia hosiei. Their flat structures were established by mass spectrometry and by a combination of NMR experiments. These molecules probably share a common biosynthetic origin with the lupin alkaloids but they differ in the formation of the last ring, being here part of a rare 2-azabicyclo[3.2.1]octane system. Their absolute configuration was determined by X-ray crystallography using CuKα radiation. As has been described for cytisine, they display a remarkable affinity towards neuronal nicotinic acetylcholine α4β2 receptor.
Published: 2014
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15. Dosage-dependent regulation of cell proliferation and adhesion through dual β2-adrenergic receptor/cAMP signals

Author: Ariana Bruzzone, Aude Saulière, Frédéric Finana, Céline Galés, Isabel Alicia Luthy, Jean-Michel Senard, Simon, Marie Francoise, Instituto de Biología y Medicina Experimental [Buenos Aires] (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biologie Moléculaire et Cellulaire, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pharmacologie Clinique, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]
Subjects: Agonist, MESH: Signal Transduction, CIENCIAS MÉDICAS Y DE LA SALUD, MESH: Cell Line, Tumor, medicine.drug_class, Epac, Population, SIGNALING COMPARTMENTALIZATION, Biochemistry, MESH: Cell Adhesion, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, signaling compartmentalization, MESH: Cell Proliferation, Cell Adhesion, Cyclic AMP, Genetics, medicine, Humans, PKA, Cell adhesion, education, Receptor, Molecular Biology, MESH: Cyclic AMP, Cell Proliferation, 030304 developmental biology, 0303 health sciences, education.field_of_study, MESH: Humans, EPAC, Cell growth, Chemistry, MCF-10A human breast cell line, MCF-10A, Adhesion, Bioquímica y Biología Molecular, Molecular biology, Medicina Básica, Cell culture, 030220 oncology & carcinogenesis, Phosphorylation, Receptors, Adrenergic, beta-2, HUMAN BREAST CELL LINE, MESH: Receptors, Adrenergic, beta-2, Signal Transduction, Biotechnology
Abstract: The role of Beta-adrenergic receptors (B-ARs) remains controversial in normal and tumor breast. Herein we explore the cAMP signaling involved in B-AR-dependent control of proliferation and adhesion of nontumor human breast cell line MCF-10A. Low concentrations of a B-agonist, isoproterenol (ISO), promote cell adhesion (87.5% cells remaining adherent to the plastic dishes following specific detachment vs. 35.0% in control, P 0.001), while increasing concentrations further engages an additional 36% inhibition of Erk1/2 phosphorylation (p-Erk1/2) -dependent cell proliferation (P 0.01). Isoproterenol dose response on cell adhesion was fitted to a 2-site curve (EC50(1): 16.5 +/-11.5 fM, EC50(2): 4.08 +/- 3.09 nM), while ISO significantly inhibited p-Erk1/2 according to a 1-site model (EC50: 0.25 +/- 0.13 nM). Using B-AR-selective agonist/antagonists and cAMP analogs/inhibitors, we identified a dosage-dependent signaling in which low ISO concentrations target a B2-AR population localized in raft microdomains and stimulate a Gs/cAMP/Epac/adhesion-signaling module, while higher concentrations engage a concomitant activation of another B2-AR population outside rafts and inhibit the proliferation by a Gs/cAMP/PKA-dependent signaling module. Our data provide a new molecular basis for the dose-dependent switch of B-AR signaling. This study also sheds light on a new cAMP pathway core mechanism with a single receptor triggering dual cAMP signaling controlled by PKA or Epac but with different cellular outputs. Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Saulière, Aude. Inserm; Francia Fil: Finana, Frédéric . Institut de Recherche Pierre Fabre; Francia Fil: Sénard, Jean Michel. Inserm; Francia. Toulouse University Hospital; Francia Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Galés, Céline. Inserm; Francia
Published: 2014
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16. 4-Hydroxynonenal impairs transforming growth factor-β1-induced elastin synthesis via epidermal growth factor receptor activation in human and murine fibroblasts

Author: Pauline Larroque-Cardoso, Anne-Marie Schmitt, Elodie Mucher, Marie-Hélène Grazide, Robert Salvayre, Gwendal Josse, Florence Nadal-Wolbold, Anne Nègre-Salvayre, Kamelija Zarkovic, Negre-Salvayre, Anne, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Pierre Fabre Dermo-Cosmétique, Pierre Fabre Applied Skin Research Centre, Department of Neuropathology, University of Zagreb-Clinical Hospital Center Zagreb, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Division of Pathology, KBC Zagreb-Clinical Hospital Centre, and Centre de Recherche Pierre Fabre
Subjects: Adult, MAPK/ERK pathway, Aging, [SDV]Life Sciences [q-bio], Primary Cell Culture, Smad2 Protein, SMAD, Biochemistry, Transforming Growth Factor beta1, Mice, Lipid oxidation, Physiology (medical), Animals, Humans, Smad3 Protein, Aorta, ComputingMilieux_MISCELLANEOUS, Cell Line, Transformed, Flavonoids, Homeodomain Proteins, Mitogen-Activated Protein Kinase 1, Aldehydes, Mitogen-Activated Protein Kinase 3, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Tropoelastin, biology, Chemistry, 4-Hydroxynonenal, TGF-β1, EGF receptor, Fibroblasts, Free radicals, Tyrphostins, Molecular biology, Elastin, Cell biology, ErbB Receptors, Repressor Proteins, [SDV] Life Sciences [q-bio], Protein Transport, Gene Expression Regulation, Quinazolines, biology.protein, Phosphorylation, Lipid Peroxidation, Signal transduction, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction, Transforming growth factor
Abstract: International audience; Elastin is a long-lived protein and a key component of connective tissues. The tissular elastin content decreases during chronological aging, and the mechanisms underlying its slow repair are not known. Lipid oxidation products that accumulate in aged tissues may generate protein dysfunction. We hypothesized that 4-hydroxynonenal (4-HNE), a highly reactive α,β-aldehydic product generated from polyunsaturated fatty acid peroxidation, could contribute to inhibiting elastin repair by antagonizing the elastogenic signaling of transforming growth factor-β1 (TGF-β1) in skin fibroblasts. We report that a low 4-HNE concentration (2µmol/L) inhibits the upregulation of tropoelastin expression stimulated by TGF-β1 in human and murine fibroblasts. The study of signaling pathways potentially involved in the regulation of elastin expression showed that 4-HNE did not block the phosphorylation of Smad3, an early step of TGF-β1 signaling, but inhibited the nuclear translocation of Smad2. Concomitantly, 4-HNE modified and stimulated the phosphorylation of the epidermal growth factor receptor (EGFR) and subsequently ERK1/2 activation, leading to the phosphorylation/stabilization of the Smad transcriptional corepressor TGIF, which antagonizes TGF-β1 signaling. Inhibitors of EGFR (AG1478) and MEK/ERK (PD98059), and EGFR-specific siRNAs, reversed the inhibitory effect of 4-HNE on TGF-β1-induced nuclear translocation of Smad2 and tropoelastin synthesis. In vivo studies on aortas from aged C57BL/6 mice showed that EGFR is modified by 4-HNE, in correlation with an increased 4-HNE-adduct accumulation and decreased elastin content. Altogether, these data suggest that 4-HNE inhibits the elastogenic activity of TGF-β1, by modifying and activating the EGFR/ERK/TGIF pathway, which may contribute to altering elastin repair in chronological aging and oxidative stress-associated aging processes.
Published: 2014
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17. Elaboration of integrated microelectrodes for the detection of antioxidant species

Author: Jérôme Launay, Pierre Temple-Boyer, Celine Christophe, Pierre Gros, Emmanuel Questel, Fadhila Sekli-Belaidi, Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Équipe MICrosystèmes d'Analyse (LAAS-MICA), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de génie chimique [ancien site de Basso-Cambo] (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Centre de recherche sur la peau, PIERRE FABRE, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National des Sciences Appliquées de Toulouse - INSA (FRANCE), Institut Supérieur de l'Aéronautique et de l'Espace - ISAE-SUPAERO (FRANCE), Laboratoires Pierre Fabre (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université Toulouse - Jean Jaurès - UT2J (FRANCE), Université Toulouse 1 Capitole - UT1 (FRANCE), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Laboratoire de Génie Chimique (LGC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Institut National Polytechnique de Toulouse - INPT (FRANCE)
Subjects: Auxiliary electrode, Working electrode, Passivation, Inorganic chemistry, chemistry.chemical_element, 02 engineering and technology, Electrochemistry, 01 natural sciences, Reference electrode, Silver chloride, chemistry.chemical_compound, [CHIM.GENI]Chemical Sciences/Chemical engineering, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Antioxidant species, Materials Chemistry, Génie chimique, SU-8 passivation, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Electrical and Electronic Engineering, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Génie des procédés, Instrumentation, 010401 analytical chemistry, Metals and Alloys, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, chemistry, Oxidative stress, Electrochemical properties, Thin-film microelectrodes, Cyclic voltammetry, 0210 nano-technology, Platinum
Abstract: International audience; (Pt-Pt-Ag/AgCl) and (Au-Pt-Ag/AgCl) electrochemical microcells (ElecCell) were developed for the detection of redox species by cyclic voltammetry. A special emphasis was placed on the SU-8 waferlevel passivation process in order to optimize the electrochemical properties of the different âthin filmâ metallic layers, i.e. gold or platinum for the working electrode, platinum for the counter electrode and silver/silver chloride for the reference electrode. (AuâPtâAg/AgCl) microcells were applied for the detection of antioxidant species such as ascorbic and uric acids in phosphate buffer solution, evidencing high sensitivity but low selectivity. Works were extended to skin analysis, demonstrating that a good electrical contact with the skin hydrolipidic film allowed the effective evaluation of the skin global antioxidant capacity.
Published: 2013
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18. Radiosynthesis and Preclinical Evaluation of 18F-F13714 as a Fluorinated 5-HT1A Receptor Agonist Radioligand for PET Neuroimaging

Author: Sophie Lancelot, Bernard Vacher, Guillaume Becker, Laetitia Lemoine, Adrian Newman-Tancredi, Luc Zimmer, Thierry Billard, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de recherches Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Agonist, Fluorine Radioisotopes, medicine.drug_class, Aminopyridines, Pharmacology, Rats, Sprague-Dawley, Radioligand Assay, 03 medical and health sciences, 0302 clinical medicine, Piperidines, In vivo, Radioligand, medicine, Animals, Radiology, Nuclear Medicine and imaging, Receptor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Chemistry, Brain, Serotonin 5-HT1 Receptor Agonists, Rats, Isotope Labeling, Positron-Emission Tomography, Receptor, Serotonin, 5-HT1A, Cats, 5-HT1A receptor, Serotonin, Radiopharmaceuticals, 030217 neurology & neurosurgery, Ex vivo, Endogenous agonist
Abstract: PET brain imaging of the serotonin 1A (5-hydroxytryptamine 1A [5-HT(1A)]) receptor has been widely used in clinical studies. Currently, only a few well-validated radiolabeled antagonist tracers are available for in vivo imaging of this central receptor. 5-HT(1A) receptors exist in high- and low-affinity states, depending on their coupling to G proteins. Agonists bind preferentially to receptors in the high-affinity state and thereby could provide a measure of functional 5-HT(1A) receptors. Therefore, it is of great interest to develop an (18)F-labeled full agonist 5-HT(1A) receptor radiotracer. In this study, we radiolabeled the high-affinity 5-HT(1A) receptor agonist (18)F-F13714 and investigated its potential as a PET tracer.F13714 nitro precursor was synthesized and radiolabeled via a fluoronucleophilic substitution. In vitro binding assays were performed using established protocols. Radiopharmacologic evaluations included in vitro autoradiography in rat brain and PET scans on anesthetized cats.The chemical and radiochemical purities of (18)F-F13714 were greater than 98%. F13714 has a high affinity (0.1 nM) and selectivity for 5-HT(1A) receptors. In vitro (18)F-F13714 binding in rats was consistent with the known 5-HT(1A) receptors distribution (hippocampus and cortical areas) and was particularly high in the dorsal raphe. In vitro binding of (18)F-F13714 was blocked in a dose-dependent fashion by WAY100635, the prototypical 5-HT(1A) antagonist, and by the endogenous agonist, serotonin (5-HT). Addition of Gpp(NH)p also inhibited in vitro (18)F-F13714 binding, consistent with a preferential binding of the compound to G-protein-coupled receptors. Ex vivo tissue measurements in rat revealed an absence of brain radioactive metabolites. In vivo studies showed that the radiotracer entered the cat brain readily and displayed a preferential labeling of 5-HT(1A) receptors located in cingulate cortex. In vivo labeling was prevented by preinjection of WAY100635.(18)F-F13714 is a radiofluorinated agonist that presents suitable characteristics for probing the high-affinity states of the 5-HT(1A) receptors in vitro and in vivo. Thus, it is a promising tool for investigation of 5-HT(1A) agonist binding in the living human brain.
Published: 2012
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19. Viable skin efficiently absorbs and metabolizes bisphenol A

Author: Sandrine Bruel, Daniel Zalko, Hélène Duplan, Elisabeth Perdu, Carine Jacques, Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire de Pharmacocinétique Cutanée (LABORATOIRE DE PHARMACOCINéTIQUE CUTANéE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Zalko, Daniel, Jacques, Carine, Duplan, Hélène, Bruel, Sandrine, and Perdu, Elisabeth
Subjects: Bisphenol A, Swine, Health, Toxicology and Mutagenesis, Human skin, Endocrine Disruptors, 010501 environmental sciences, 01 natural sciences, Toxicology, chemistry.chemical_compound, Biotransformation, Carbon Radioisotopes, Milieux et Changements globaux, perturbateur endocrinien, 0303 health sciences, integumentary system, Chemistry, General Medicine, Pollution, dermal absorption, Dose–response relationship, Radioactivity, Female, biotransformation, hormones, hormone substitutes, and hormone antagonists, Adult, endocrine system, skin, Environmental Engineering, [SDE.MCG]Environmental Sciences/Global Changes, In Vitro Techniques, Models, Biological, bpa, Pig skin, 03 medical and health sciences, Phenols, Animals, Humans, Environmental Chemistry, human, Benzhydryl Compounds, 030304 developmental biology, 0105 earth and related environmental sciences, Chromatography, Dose-Response Relationship, Drug, urogenital system, Public Health, Environmental and Occupational Health, General Chemistry, Metabolism, Human exposure, peau, endocrine disrupter, Xenobiotic, humain
Abstract: International audience; Skin contact has been hypothesized to contribute to human exposure to bisphenol A (BPA). We examinedthe diffusion and metabolism of BPA using viable skin models: human skin explants and short-term culturesof pig ear skin, an alternative model for the study of the fate of xenobiotics following contact exposure.14C-BPA [50–800 nmol] was applied on the surface of skin models. Radioactivity distribution wasmeasured in all skin compartments and in the diffusion cells of static cells diffusion systems. BPA andmetabolites were further quantified by radio-HPLC. BPA was efficiently absorbed in short-term cultures,with no major difference between the models used in the study [viable pig ear skin: 65%; viable humanexplants: 46%; non-viable (previously frozen) pig skin: 58%]. BPA was extensively metabolized in viablesystems only. Major BPA metabolites produced by the skin were BPA mono-glucuronide and BPA monosulfate,accounting together for 73% and 27% of the dose, in pig and human, respectively. In conclusion,experiments with viable skin models unequivocally demonstrate that BPA is readily absorbed and metabolizedby the skin. The trans-dermal route is expected to contribute substantially to BPA exposure inhuman, when direct contact with BPA (free monomer) occurs.
Published: 2011
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20. In vitro Percutaneous Absorption and in vivo Stratum Corneum Distribution of an Organic and a Mineral Sunscreen

Author: C. Miquel, Bruno Payré, P. Moretto, O. Lejeune, A. Mavon, Laboratoire de Pharmacocinétique Cutanée (LABORATOIRE DE PHARMACOCINéTIQUE CUTANéE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Adult, Tape stripping, Physiology, Analytical chemistry, Human skin, 02 engineering and technology, Dermatology, Absorption (skin), Particle-induced X-ray emission, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, Tinosorb M, 0302 clinical medicine, Microscopy, Electron, Transmission, Dermis, Skin absorption, In vivo, Stratum corneum, medicine, Electron microscopy, Humans, Tissue Distribution, Chromatography, High Pressure Liquid, Titanium, Pharmacology, integumentary system, Spectrometry, X-Ray Emission, General Medicine, Penetration (firestop), Triazoles, 021001 nanoscience & nanotechnology, In vitro, medicine.anatomical_structure, chemistry, Titanium dioxide, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Colorimetry, Female, 0210 nano-technology, Sunscreening Agents, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Biomedical engineering
Abstract: Sunscreens, whose main function is to protect the skin against the harmful effects of solar irradiation, should remain at the skin surface or impregnate the first layers of the stratum corneum only and not penetrate into the underlying living tissue. The goal of this work was to assess the penetration of titanium dioxide (TiO2) and methylene bis-benzotriazoyl tetramethylbutylphenol (MBBT), included in a broad-spectrum sunscreen formulation, into human skin in vivo, using the tape stripping method, and in vitro, using a compartmental approach. An additional objective was to propose an easy and minimally invasive approach to determining the percutaneous uptake of sunscreens following topical application. TiO2 and MBBT were quantified using colorimetric assay and HPLC analysis, respectively. The transmission electron microscopy and particle-induced X-ray emission techniques were used to localize the TiO2 in skin sections.More than 90% of both sunscreens was recovered in the first 15 tape strippings. In addition we have shown that the remaining 10% did not penetrate the viable tissue, but was localized in the furrows and in the opened infundibulum. Less than 0.1% of MBBT was detected in the receptor medium, and no TiO2 was detected in the follicle, viable epidermis or dermis. Thus, this in vivo and in vitro penetration study showed an absence of TiO2 penetration into the viable skin layers through either transcorneal or transfollicular pathways and negligible transcutaneous absorption of MBBT. However, differences in distribution within the stratum corneum reinforced the need for a complementary approach, using minimally invasive in vivo methodology and in vitro compartmental analysis.This combination represents a well-adapted method for testing the safety of topically applied sunscreen formulations in real-life conditions.
Published: 2007
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21. Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drug

Author: Jean-Paul Ribet, Marie Lorin, Philippe Morin, Raphaël Delépée, Jean-Claude Maurizot, Institut de Chimie Organique et Analytique (ICOA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Circular dichroism, enantiomeric purity, Resolution (mass spectrometry), Calibration curve, Analytical chemistry, 2-adrenoreceptor antagonist, 010501 environmental sciences, Sensitivity and Specificity, 01 natural sciences, High-performance liquid chromatography, Concentration ratio, Catalysis, Analytical Chemistry, Drug Discovery, Adrenergic alpha-Antagonists, Chromatography, High Pressure Liquid, Spectroscopy, Benzofurans, 0105 earth and related environmental sciences, Pharmacology, Detection limit, low-pass electronic noise filter, Chromatography, quantitation, Chemistry, 010401 analytical chemistry, Organic Chemistry, Imidazoles, Stereoisomerism, Repeatability, 0104 chemical sciences, circular dichroism, efaroxan, Enantiomer, HPLC, polysaccharide stationary phase
Abstract: The quality control of chiral drugs requires the determination of their enantiomeric purity. Nowadays, circular dichroism (CD) spectroscopy is gaining increasing importance in pharmaceutical analysis because of the commercially available CD detector in liquid chromatography. The separation of the two enantiomers of a basic drug (efaroxan) was achieved by high performance liquid chromatography using an amylose-derivated column with both UV and CD detections. A baseline-resolved separation (resolution: 5) was obtained after optimization of the mobile phase composition with hexane-ethanol-diethylamine (90:10:0.05; v/v/v). The use of a commercial low-pass electronic noise filter of the CD signal has improved the signal-to-noise ratio by a factor twelve and allowed the quantitation of each enantiomer in the 1.25-300 microg ml(-1) concentration range. The CD linear calibration curve, expressed in terms of stereoisomer height ratio versus concentration ratio, was plotted over the 0.4-6% range. A correlation coefficient greater than 0.999 was obtained by least-squares regression and the limit of detection for the distomer/eutomer ratio was estimated at 0.14%. Although the method validation showed good repeatability on the retention times (RSD0.9%), on the peak height ratios (RSD8.7%) of each enantiomer only up to 99.2% enantiomeric purity was achieved.
Published: 2007
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22. Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp

Author: Olivier Lozach, Laurent Meijer, Arnaud Parenty, Dominique Laurent, Frédéric Alby, Nicolas Lebouvier, Christian Doerig, Martine Knibiehler, Maryvonne Frostin, Séverine Maurel, Sophie Schmitt, Dominique Dorin, Valérie Jullian, Michel Sauvain, Institut Non Linéaire de Nice Sophia-Antipolis (INLN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique de la matière condensée (LPMC), Pharmacochimie des substances naturelles et pharmacophores redox, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire des Substances Naturelles, Synapse Développement, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Insulaire du Vivant et de l'Environnement (LIVE), Université de la Nouvelle-Calédonie (UNC), UMS 2646 Pierre Fabre-CNRS, Institut de Sciences et Technologies du Médicament de Toulouse, 3, rue des satellites, 31400 Toulouse, France, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Controle de la Proliferation Cellulaire Chez Plasmodium Falciparum, Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Epistémologiques et Historiques sur les Sciences Exactes et les Institutions Scientifiques (REHSEIS (UMR_7596)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS), UMS 2646, PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mer et santé (MS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre Fabre-Centre National de la Recherche Scientifique (CNRS), faculte des sciences pharmaceutiques (umr 152 IRD), Faculte des Sciences Pharmaceutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and BUNC, Pole ID
Subjects: antiplasmodial drug, Plasmodium, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Pharmaceutical Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacognosy, 01 natural sciences, Biochemistry, Mice, chemistry.chemical_compound, Antimalarial drug, Drug Discovery, MESH: Protein Kinase Inhibitors, MESH: Animals, MESH: Plasmodium falciparum, MESH: Inhibitory Concentration 50, 0303 health sciences, biology, Kinase, Quinones, Biological activity, 3. Good health, Xestospongia, [SDV] Life Sciences [q-bio], Enzyme inhibitor, Molecular Medicine, Biological Assay, Antiplasmodial drug, antimalarial drug, Plasmodium falciparum, MESH: Biological Assay, MESH: Quinones, Antimalarials, Inhibitory Concentration 50, 03 medical and health sciences, parasitic diseases, Animals, Xestoquinone, Plasmodium berghei, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein kinase A, Protein Kinase Inhibitors, Molecular Biology, MESH: Mice, 030304 developmental biology, 010405 organic chemistry, Organic Chemistry, biology.organism_classification, MESH: Antimalarials, 0104 chemical sciences, MESH: Xestospongia, xestoquinone, chemistry, biology.protein
Abstract: As part of our search for new antimalarial drugs, we have screened for inhibitors of Pfnek-1, a protein kinase of Plasmodium falciparum, in south Pacific marine sponges. On the basis of a preliminary screening, the ethanolic crude extract of a new species of Xestospongia collected in Vanuatu was selected for its promising activity. A bioassay-guided fractionation led us to isolate xestoquinone which inhibits Pfnek-1 with an IC50 around 1 mu M. Among a small panel of plasmodial protein kinases, xestoquinone showed modest protein kinase inhibitory activity toward PfPK5 and no activity toward PfPK7 and PfGSK-3. Xestoquinone showed in vitro antiplasmodial activity against a FCB1 P. falciparum strain with an IC50 of 3 mu M and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5 mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses. (c) 2006 Elsevier Ltd. All rights reserved.
Published: 2006
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23. HPLC quantitation of the four stereoisomers of benzoxathiepin derivatives with cellulose phenyl type chiral stationary phase and circular dichroism detection

Author: Philippe Morin, Martine Beaufour, Jean-Claude Maurizot, Jean-Paul Ribet, Institut de Chimie Organique et Analytique (ICOA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Département de Chimie Analytique (PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Circular dichroism, chiral separation, Clinical Biochemistry, Pharmaceutical Science, Stereoisomerism, 010501 environmental sciences, 01 natural sciences, High-performance liquid chromatography, Analytical Chemistry, Stereocenter, chemistry.chemical_compound, Phase (matter), Spectrophotometry, Drug Discovery, medicine, Cellulose, Chromatography, High Pressure Liquid, Spectroscopy, 0105 earth and related environmental sciences, Detection limit, Chromatography, medicine.diagnostic_test, benzoxathiepins, derivatised cellulose, basic drug, 010401 analytical chemistry, Reproducibility of Results, 0104 chemical sciences, circular dichroism, chemistry, Spectrophotometry, Ultraviolet, Serotonin Antagonists, Thiepins, HPLC
Abstract: The chiral separation of a new antianginal agent has been investigated on a chiral cellulose column with UV and circular dichroism (CD) detection. This benzoxathiepin derivative under development has two stereogenic centers whose (R,S) stereoisomer shows an interesting antianginal activity. After optimisation of the mobile phase composition, a baseline-resolved separation of the four stereoisomers was achieved on a Chiralcel OJ-H chiral column by using methanol-ethanol-diethylamine (25:75:0.1, v/v/v) as mobile phase. The CD detection system allowed quantitation and a linear response was observed within a 10-200 microg mL-1 concentration range (r2=0.9966) and limit of quantification down to 2 microg mL-1 was achieved.
Published: 2006
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24. Comparative study between reconstructed and native human epidermis using nuclear microscopy

Author: M. Rosdy, Philippe Moretto, Etienne Gontier, M.D. Ynsa, Alain Mavon, Dirk E. Boerma, Aurelio Climent-Font and Miguel Ángel Respaldiza, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, SkinEthic Laboratories (SKINETHIC LABORATORIES), and SkinEthic Laboratories
Subjects: Nuclear and High Energy Physics, Microprobe, Micro pixe, Analytical chemistry, Human skin, 01 natural sciences, Skin models, 03 medical and health sciences, 0302 clinical medicine, 29.30.−Kv, 87.64.−t, Native skin, Instrumentation, integumentary system, Chemistry, 010401 analytical chemistry, Nuclear microscopy, 0104 chemical sciences, Micro-PIXE, Micro-RBS, Ultrastructure, Biophysics, STIM, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Barrier effect, Epidermis, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, 030215 immunology
Abstract: International audience; The physiological status of native skin is suffering from large inter-individual variations, especially in terms of inorganic ions content. For this reason, together with the advent of ethic laws on animal experimentation, reconstructed skin or epidermis models are extensively employed nowadays in penetration studies for cosmetic or pharmacological applications. It has been already verified that reconstructed human epidermis (RHE) has similar physiological mechanisms to native human skin, but until now, there are few studies where the elemental concentrations of both skins, reconstructed and native, are compared. In this work, freeze-dried thin sections of human native skin obtained from surgery have been characterized using PIXE, RBS and STIM at the CENBG nuclear microprobe. RHE samples were treated and analyzed in the same conditions for comparison. The combination of the different imaging and analysis techniques made possible a clear delimitation and identification of skin ultrastructure. The elemental concentrations of P, S, Cl, K and Ca were measured in the different strata. For both skins, concentrations have been compared and significant differences in terms of elemental concentrations have been determined using statistical approaches. Similar physiological characteristics were pointed out in both skin models, in particular the Ca gradient presumably involved in the regulation of the barrier effect.
Published: 2006
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25. Mechanisms of MoS2 formation by MoDTC in presence of ZnDTP: effect of oxidative degradation

Author: Minatchy, G., Thomas, Philippe, Bilas, Philippe, Nomède-Martyr, N., Romana, Laurence, Mansot, Jean-Louis, Legras, Laurent, Dubois, Marc, Hamwi, André, Guérin, Katia, Mansot, J.L., Merrifiels, M., Bercion, Y., Aranda, D. Aldana, De Barros Bouchet, Maria-Isabel, Martin, J.M., Le Mogne, Th., Vacher, B., Yamada, Y., Agence Universitaire de la Francophonie (AUF), Groupe de Technologie des Surfaces et Interfaces [URp2_2] (GTSI), Université des Antilles (UA), Université des Antilles (Pôle Guadeloupe), MI, Institut de Chimie de Clermont-Ferrand (ICCF), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Matériaux et Mécanique des Composants (EDF R&D MMC), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Institut Langevin - Ondes et Images (UMR7587) (IL), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Matériaux Inorganiques (LMI), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Clermont Université-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE)-Centre National de la Recherche Scientifique (CNRS), Centre de recherches Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Groupe de Technologie des Surfaces et Interfaces (GTSI), Institut de Chimie du CNRS (INC)-SIGMA Clermont (SIGMA Clermont)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-SIGMA Clermont (SIGMA Clermont)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Chimie du CNRS (INC)-SIGMA Clermont (SIGMA Clermont)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS)
Subjects: business.product_category, Inorganic chemistry, chemistry.chemical_element, 02 engineering and technology, Oxygen, chemistry.chemical_compound, 0203 mechanical engineering, X-ray photoelectron spectroscopy, Materials Chemistry, Lubricant, [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], Motor oil, Chemical composition, ComputingMilieux_MISCELLANEOUS, Surfaces and Interfaces, Tribology, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Nitrogen, Surfaces, Coatings and Films, 020303 mechanical engineering & transports, chemistry, Mechanics of Materials, Nitrogen oxide, 0210 nano-technology, business
Abstract: Friction-reducing properties of MoDTC-containing lubricants have been investigated as a function of their oxidative degradation state. The oxidation test is conducted with oxygen and nitrogen oxide gases simulating aged engine oils during service. The main oxidation effect is to decrease the concentrations of MoDTC and other additives present in the formulation. However, when the ZnDTP concentration is reduced in the lubricant, MoDTC is not so fast consumed because of the formation of less stable MoDTP compound by acid–base reaction is inhibited. The decrease of friction reduction properties appears significant when about 80% of additives content has been consumed by oxidation. The friction reduction mechanism of MoDTC is due to the formation of MoS 2 single sheets during the tribochemical reaction. When the concentration of MoDTC decreases in the lubricant due to oxidation, MoS 2 sheets are found to be modified both in size, number, shape and chemical composition. Final, at very low MoDTC concentration, sheets cannot grow to a sufficient size to cover the asperities for efficient friction reduction.
Published: 2005
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26. A Novel Synthetic Inhibitor of CDC25 Phosphatases

Author: Christophe Thurieau, Jeremiath Harnett, Véronique Baldin, Olivier Lavergne, Gregoire Prevost, Odile Mondesert, Philip G. Kasprzyk, Christophe Lanco, Frédéric Alby, Marie-Christine Brezak, Muriel Quaranta, Martine Cazales, Marie-Odile Galcera, Bernard Ducommun, Institut Henri Beaufour (IPSEN), IPSEN-BEAUFOUR, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), UMS 2646 Pierre Fabre-CNRS, Institut de Sciences et Technologies du Médicament de Toulouse, 3, rue des satellites, 31400 Toulouse, France, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Centre de recherches de biochimie macromoléculaire (CRBM), and Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, CDC25A, Cell cycle checkpoint, Cdc25, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], HeLa, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cyclin, 0303 health sciences, biology, Kinase, Tyrosine phosphorylation, Cell cycle, biology.organism_classification, 3. Good health, Cell biology, enzymes and coenzymes (carbohydrates), Oncology, chemistry, 030220 oncology & carcinogenesis, biology.protein, biological phenomena, cell phenomena, and immunity
Abstract: CDC25 dual-specificity phosphatases are essential regulators that dephosphorylate and activate cyclin-dependent kinase/cyclin complexes at key transitions of the cell cycle. CDC25 activity is currently considered to be an interesting target for the development of new antiproliferative agents. Here we report the identification of a new CDC25 inhibitor and the characterization of its effects at the molecular and cellular levels, and in animal models. BN82002 inhibits the phosphatase activity of recombinant human CDC25A, B, and C in vitro. It impairs the proliferation of tumoral cell lines and increases cyclin-dependent kinase 1 inhibitory tyrosine phosphorylation. In synchronized HeLa cells, BN82002 delays cell cycle progression at G1-S, in S phase and at the G2-M transition. In contrast, BN82002 arrests U2OS cell cycle mostly in the G1 phase. Selectivity of this inhibitor is demonstrated: (a) by the reversion of the mitotic-inducing effect observed in HeLa cells upon CDC25B overexpression; and (b) by the partial reversion of cell cycle arrest in U2OS expressing CDC25. We also show that BN82002 reduces growth rate of human tumor xenografts in athymic nude mice. BN82002 is a original CDC25 inhibitor that is active both in cell and animal models. This greatly reinforces the interest in CDC25 as an anticancer target.
Published: 2004
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27. Unrepaired cyclobutane pyrimidine dimers do not prevent proliferation of UV-B-irradiated cultured human fibroblasts

Author: Caroline Baudouin, Thierry Douki, Stéphane Mouret, Jean Cadet, Alain Favier, Sophie Courdavault, Sylvie Sauvaigo, Serge M. Candéias, Marie Charveron, Laboratoires Expanscience, Laboratoires Expanscience, R&D, LXRepair, Institut de Recherche Biomédicale des Armées (IRBA), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Biologie Cellulaire Cutanée, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), and Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: Time Factors, DNA Repair, DNA damage, Stereochemistry, Ultraviolet Rays, education, Pyrimidine dimer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010402 general chemistry, 01 natural sciences, Biochemistry, Mass Spectrometry, Cyclobutane, Flow cytometry, chemistry.chemical_compound, 03 medical and health sciences, medicine, Humans, Physical and Theoretical Chemistry, Cytotoxicity, Carcinogen, Cells, Cultured, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, Chemistry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Dose-Response Relationship, Radiation, General Medicine, DNA, Fibroblasts, Molecular biology, Deoxyuridine, 0104 chemical sciences, Bromodeoxyuridine, Mutagenesis, Pyrimidine Dimers, Cell Division, DNA Damage
Abstract: International audience; Mutagenic and carcinogenic UV-B radiation is known to damage DNA mostly through the formation of bipyrimidine photoproducts, including cyclobutane dimers (CPD) and (6-4) photoproducts ((6-4) PP). Using high-performance liquid chromatography coupled to tandem mass spectrometry, we investigated the formation and repair of thymine-thymine (TT) and thymine-cytosine (TC) CPD and (6-4) PP in the DNA of cultured human dermal fibroblasts. A major observation was that the rate of repair of the photoproducts did not depend on the identity of the modified pyrimidines. In addition, removal of CPD was found to significantly decrease with increasing applied UV-B dose, whereas (6-4) PP were efficiently repaired within less than 24 h, irrespective of the dose. As a result, a relatively large amount of CPD remained in the genome 48 h after the irradiation. Because the overall applied doses (
Published: 2004

28. Bioactive flavonoids of Tanacetum parthenium revisited

Author: Christophe Long, Frédéric Ausseil, Bruno David, Georges Massiot, Catherine Lavaud, Pierre Sauleau, Valerie Cassabois, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Laboratoire de Pharmacognosie, Université de Reims Champagne-Ardenne (URCA), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0106 biological sciences, Jaceidin, Flavonols, Flavonoid, Mitosis, Antineoplastic Agents, Plant Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Horticulture, Biology, Chemical Fractionation, Tanacetum parthenium, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Inhibitory Concentration 50, Botany, medicine, Inhibitory concentration 50, Animals, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Confusion, chemistry.chemical_classification, Flavonoids, Centaureidin, Traditional medicine, 010405 organic chemistry, Plant Extracts, General Medicine, 0104 chemical sciences, 3. Good health, 010404 medicinal & biomolecular chemistry, chemistry, medicine.symptom, 010606 plant biology & botany
Abstract: Bio-guided fractionation of an extract from Tanacetum parthenium showing activity as mitotic blocker allowed the isolation and identification of santin 3, jaceidin 2 and centaureidin 1. The latter two closely related flavonols, which, to the best of our knowledge, are isolated here together for the first time, form a mixture difficult to resolve and which is probably the reason for the confusion in the literature regarding their occurrence. Centaureidin 1 had an IC50 of 1 microM while jaceidin 2 and santin 3 were 200 times less active.
Published: 2003
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29. Elastin Modification by 4-Hydroxynonenal in Hairless Mice Exposed to UV-A. Role in Photoaging and Actinic Elastosis

Author: Florence Nadal-Wollbold, Mélanie Pucelle, Pauline Larroque-Cardoso, Marie Hélène Grazide, Gwendal Josse, Koji Uchida, Anne-Marie Schmitt, Patrick Bogdanowicz, Kamelija Zarkovic, Robert Salvayre, Anne Nègre-Salvayre, Caroline Camaré, Sandra Garoby-Salom, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoires Pierre Fabre, Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre, Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences-Nagoya University, Department of Neuropathology, University of Zagreb-Clinical Hospital Center Zagreb, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: medicine.medical_specialty, Ultraviolet Rays, Photoaging, [SDV]Life Sciences [q-bio], Dermatology, medicine.disease_cause, Sensitivity and Specificity, Biochemistry, 4-Hydroxynonenal, Lipid peroxidation, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, Mice, Random Allocation, 0302 clinical medicine, 4-hydroxynonenal, photoaging, elastin, medicine, Animals, Photosensitivity Disorders, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Aldehydes, Mice, Hairless, biology, Carnosine, Acrolein, Cell Biology, Actinic elastosis, medicine.disease, Elasticity, 3. Good health, Hairless, Elastin, Skin Aging, Disease Models, Animal, Oxidative Stress, chemistry, biology.protein, Lipid Peroxidation, Oxidative stress
Abstract: Chronic exposure to ultraviolet (UV) radiation causes oxidative stress, which is involved in photoaging and actinic elastosis. UV and reactive oxygen species generate lipid peroxidation products, including the α, β- unsaturated carbonyl compounds such as acrolein or 4-hydroxynonenal (4-HNE). These aldehydes can modify proteins of the extracellular matrix, but their role in the pathogenesis of photoaging is not clarified. The aim of this study was to investigate whether these aldehydes contribute to alter elastin metabolism and whether topical carbonyl scavengers delay UV-induced skin photoaging. Hairless mice (4–6-week old) daily exposed to UV-A (20Jcm-2 per day, up to 600Jcm-2) exhibited the typical features of photoaging, associated with a significant increase in 4-HNE- and acrolein-adduct content, and elastotic material deposition. Immunofluorescence studies showed the accumulation of 4-HNE adducts on elastin in the dermis of UV-A-exposed mice. This was mimicked in vitro by incubating orcein-elastin with 4-HNE or acrolein, which altered its digestion by leukocyte-elastase, a feature possibly involved in the accumulation of elastotic material. A daily topical application of carnosine completely reversed the development of photoaging alterations and 4-HNE-adduct formation on elastin. These data emphasize the role of 4-HNE and acrolein in the mechanism of photoaging, and the preventive effect of carbonyl scavengers.
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30. The skin barrier function : a micro-PIXE study

Author: Marina Simon, Hervé Seznec, A. Mavon, Philippe Moretto, D. Bacqueville, Philippe Barberet, Le Noan, Ludovic, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Université Sciences et Technologies - Bordeaux 1, and Institut de Recherche Pierre Fabre - Laboratoire de Pharmacocinétique Cutanée
Subjects: Micro pixe, Chemical compound, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Skin physiology, Analytical chemistry, Human skin, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, NUCLEAR MICROPROBE, PERCUTANEOUS-ABSORPTION, EPIDERMIS, IN-VIVO, Spectroscopy, Barrier function, Skin barrier function, 030304 developmental biology, DAMAGE, 0303 health sciences, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Chemistry, STRATUM-CORNEUM, Penetration (firestop), 3. Good health, MICROANALYSIS, Ion homeostasis, Biophysics
Abstract: Human body is perpetually subjected to environmental exposures as sun, natural, urban or industrial pollutions and societal exposures. Skin is the main physiological barrier facing to these different stresses; however its response mechanisms are still not well understood. Skin models are thus necessary to understand skin physiology and behavior in normal conditions or under stress. Because of the large natural interindividual variability and of some difficulties in obtaining human skin biopsies, we have been developing and characterizing different skin models such as reconstructed epidermis in vitro, native pigskin and human keratinocyte cells. These models allow us to study the mechanisms involved in ion homeostasis in correlation with structural organization and biological responses. In the present study, we have characterized the pig ear skin model using micro-particle induced x-ray emission (PIXE) analysis with the aim of evaluating the distribution of inorganic ions under normal or stress conditions together with the transepidermal penetration of external agents, such as aluminum oxides. The nuclear microprobe analysis allowed us to validate the culture conditions of the tissue and we have shown an alteration of the inorganic ion patterns after exposure to a chemical compound (sodium dodecyl sulfate) known for its deleterious effects on the barrier function. Finally, we have shown no transepidermal penetration of aluminum oxides after different exposures to cosmetic formulations. Copyright (C) 2009 John Wiley & Sons, Ltd.
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30 results on '"FABRE, PIERRE"'

1. Intake Estimation of Phytochemicals in a French Well-Balanced Diet

2. Dereplication of Natural Extracts Diluted in Glycerin: Physical Suppression of Glycerin by Centrifugal Partition Chromatography Combined with Presaturation of Solvent Signals in 13C-Nuclear Magnetic Resonance Spectroscopy

3. Taxonomically informed metabolite annotation and data organization in natural products research

4. Stabilization of microtubules restores barrier function after cytokine-induced defects in reconstructed human epidermis

5. The use of suction blisters to measure sunscreen protection against UVR- induced DNA damage

6. Editor’s Highlight: Fragrance Allergens Linalool and Limonene Allylic Hydroperoxides in Skin Allergy: Mechanisms of Action Focusing on Transcription Factor Nrf2

7. Chemical analysis and potential endocrine activities of aluminium coatings intended to be in contact with cosmetic water

8. Identification of ageing biomarkers in human dermis biopsies by thermal analysis (DSC) combined with Fourier transform infrared spectroscopy (FTIR/ATR)

9. Characterization of xenobiotic metabolizing enzymes of a reconstructed human epidermal model from adult hair follicles

10. Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors

11. Characterisation of B(a)P metabolites formed in an ex vivo pig skin model using three complementary analytical methods

12. A Myrtus communis extract enriched in myrtucummulones and ursolic acid reduces resistance of Propionibacterium acnes biofilms to antibiotics used in acne vulgaris

13. Acefylline activates filaggrin deimination by peptidylarginine deiminases in the upper epidermis

14. Cytisine-like alkaloids from Ormosia hosiei Hemsl.E.H. Wilson

15. Dosage-dependent regulation of cell proliferation and adhesion through dual β2-adrenergic receptor/cAMP signals

16. 4-Hydroxynonenal impairs transforming growth factor-β1-induced elastin synthesis via epidermal growth factor receptor activation in human and murine fibroblasts

17. Elaboration of integrated microelectrodes for the detection of antioxidant species

18. Radiosynthesis and Preclinical Evaluation of 18F-F13714 as a Fluorinated 5-HT1A Receptor Agonist Radioligand for PET Neuroimaging

19. Viable skin efficiently absorbs and metabolizes bisphenol A

20. In vitro Percutaneous Absorption and in vivo Stratum Corneum Distribution of an Organic and a Mineral Sunscreen

21. Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drug

22. Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp

23. HPLC quantitation of the four stereoisomers of benzoxathiepin derivatives with cellulose phenyl type chiral stationary phase and circular dichroism detection

24. Comparative study between reconstructed and native human epidermis using nuclear microscopy

25. Mechanisms of MoS2 formation by MoDTC in presence of ZnDTP: effect of oxidative degradation

26. A Novel Synthetic Inhibitor of CDC25 Phosphatases

27. Unrepaired cyclobutane pyrimidine dimers do not prevent proliferation of UV-B-irradiated cultured human fibroblasts

28. Bioactive flavonoids of Tanacetum parthenium revisited

29. Elastin Modification by 4-Hydroxynonenal in Hairless Mice Exposed to UV-A. Role in Photoaging and Actinic Elastosis

30. The skin barrier function : a micro-PIXE study

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