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Aluminum chlorohydrate (ACH) is a major aerosol component frequently used as the active ingredient in antiperspirants, and in vivo studies have raised a concern about its inhalation toxicity. Still, few studies have addressed its effects on the human respiratory tract. Therefore, we developed a study on ACH inhalation toxicity using an in vitro human alveolar cell model (A549 cells) with molecular and cellular markers of oxidative stress, immunotoxicity, and epigenetic changes. The chemical characterization of ACH suspensions indicated particle instability and aggregation; however, side-scatter analysis demonstrated significant particle uptake in cells exposed to ACH. Exposure of A549 cells to non-cytotoxic concentrations of ACH (0.25, 0.5, and 1 mg/ml) showed that ACH induced reactive oxygen species. Moreover, ACH upregulated TNF, IL6, IL8, and IL1A genes, but not the lncRNAs NEAT1 and MALAT1. Finally, no alterations on the global DNA methylation pattern (5-methylcytosine and 5-hydroxymethylcytosine) or the phosphorylation of histone H2AX (γ-H2AX) were observed. Our data suggest that ACH may induce oxidative stress and inflammation on alveolar cells, and A549 cells may be useful to identify cellular and molecular events that may be associated with adverse effects on the lungs. Still, further research is needed to ensure the inhalation safety of ACH.

The continuous search for natural products that attenuate age-related losses has increasingly gained notice; among them, those applicable for skin care have drawn significant attention. The bioester generated from the Chenopodium quinoa’s oil is a natural-origin ingredient described to produce replenishing skin effects. With this as motivation, we used shotgun proteomics to study the effects of quinoa bioester on human reconstructed epidermis tridimensional cell cultures after 0, 3, 6, 12, 24, and 48 h of exposure. Our experimental setup employed reversed-phase nano-chromatography coupled online with an Orbitrap-XL and PatternLab for proteomics as the data analysis tool. Extracted ion chromatograms were obtained as surrogates for relative peptide quantitation. Our findings spotlight proteins with increased abundance, as compared to the untreated cell culture counterparts at the same timepoints, that were related to preventing premature aging, homeostasis, tissue regeneration, protection against ultraviolet radiation and oxidative damage.

Every second, 0.8 litres of sunscreen enters ocean waters, which corresponds to the release of 25.000 tons per year. UV filters may present substantial threats to marine fauna and flora and have an impact similar to that of other contaminants. Coral reefs play a major role in marine biodiversity, and some publications suggest that they are threatened by the release of sunscreen into the environment, which should cause bleaching. The aim of this study was to evaluate the potential impact of sunscreen products on hard corals. Laboratory experiments in which Seriatopora hystrix coral fragments were exposed to 9 sunscreens at concentrations up to 100 mg/L for 96 hours were conducted, and the biological responses of the fragments were assessed. The examined parameters were coral bleaching and polyp retraction. The results obtained revealed that the 9 tested sunscreens had no effects on S. hystrix, with a recorded NOEC (No Observed Effect Concentration) of 100 mg/L for both tested parameters. This concentration is much higher than those of chemicals in the natural environment, which are on the order of µg/L or ng/L. Under the conditions in this experiment, the absence of toxic effects from the tested sunscreens allows us to argue the absence of potential danger on corals.

Made available in DSpace on 2021-06-25T11:12:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 The safety assessment of cosmetic products is based on the safety of the ingredients, which requires information on chemical structures, toxicological profiles, and exposure data. Approximately 6% of the population is sensitized to cosmetic ingredients, especially preservatives and fragrances. In this context, the aim of this study was to perform a hazard assessment and risk characterization of benzalkonium chloride (BAC), benzyl alcohol (BA), caprylyl glycol (CG), ethylhexylglycerin (EG), chlorphenesin (CP), dehydroacetic acid (DHA), sodium dehydroacetate (SDH), iodopropynyl butylcarbamate (IPBC), methylchloroisothiazolinone and methylisothiazolinone (MCI/MIT), methylisothiazolinone (MIT), phenoxyethanol (PE), potassium sorbate (PS), and sodium benzoate (SB). Considering the integrated approaches to testing and assessment (IATA) and weight of evidence (WoE) as a decision tree, based on published safety reports. The hazard assessment was composed of a toxicological matrix correlating the toxicity level, defined as low (L), moderate (M), or high (H) and local or systemic exposure, considering the endpoints of skin sensitization, skin irritation, eye irritation, phototoxicity, acute oral toxicity, carcinogenicity, mutagenicity/genotoxicity, and endocrine activity. In a risk assessment approach, most preservatives had a margin of safety (MoS) above 100, except for DHA, SDH, and EG, considering the worst-case scenario (100% dermal absorption). However, isolated data do not set up a safety assessment. It is necessary to carry out a rational risk characterization considering hazard and exposure assessment to estimate the level of risk of an adverse health outcome, based on the concentration in a product, frequency of use, type of product, route of exposure, body surface location, and target population. Department of Safety Assessment Grupo Boticário School of Pharmaceutical Sciences UNESP - Univ Estadual Paulista School of Pharmaceutical Sciences UNESP - Univ Estadual Paulista

The recently introduced microphysiological systems (MPS) cultivating human organoids are expected to perform better than animals in the preclinical tests phase of drug developing process because they are genetically human and recapitulate the interplay among tissues. In this study, the human intestinal barrier (emulated by a co-culture of Caco-2 and HT-29 cells) and the liver equivalent (emulated by spheroids made of differentiated HepaRG cells and human hepatic stellate cells) were integrated into a two-organ chip (2-OC) microfluidic device to assess some acetaminophen (APAP) pharmacokinetic (PK) and toxicological properties. The MPS had three assemblies: Intestine only 2-OC, Liver only 2-OC, and Intestine/Liver 2-OC with the same media perfusing both organoids. For PK assessments, we dosed the APAP in the media at preset timepoints after administering it either over the intestinal barrier (emulating the oral route) or in the media (emulating the intravenous route), at 12 µM and 2 µM respectively. The media samples were analyzed by reversed-phase high-pressure liquid chromatography (HPLC). Organoids were analyzed for gene expression, for TEER values, for protein expression and activity, and then collected, fixed, and submitted to a set of morphological evaluations. The MTT technique performed well in assessing the organoid viability, but the high content analyses (HCA) were able to detect very early toxic events in response to APAP treatment. We verified that the media flow does not significantly affect the APAP absorption whereas it significantly improves the liver equivalent functionality. The APAP human intestinal absorption and hepatic metabolism could be emulated in the MPS. The association between MPS data and in silico modeling has great potential to improve the predictability of the in vitro methods and provide better accuracy than animal models in pharmacokinetic and toxicological studies.

The cosmetic industry's growing concern about the impact of its supply chain on the environment, sustainability of raw materials, and biodiversity increases the need to ensure that the final product has a lower environmental impact. The objective of this review is to summarize and compare the information available from international organizations and legislation regarding the main criteria used to assess raw materials for aquatic toxicity, as well as the most suitable alternative methods for obtaining assessment parameters. Using the literature available in databases, a review of the scientific literature and international legislation, this work discusses and compares the parameters established by international organizations such as the Environmental Protection Agency (EPA) and Cradle to Cradle (C2C), as well as European legislation, namely, European Regulation 1272/2008, for assessing environmental impact. Defining the ecotoxicity parameters of the main classes of raw materials in rinse-off cosmetic products can enable the development of products that are more environmentally sustainable, prioritizing substances with less environmental impact.

This research work mainly deals with studying qualitatively the changes in the dermal collagen of two forms of striae distensae (SD) namely striae rubrae (SR) and striae albae (SA) when compared to normal skin (NS) using confocal Raman spectroscopy. The methodology includes an in vivo human skin study for the comparison of confocal Raman spectra of dermis region of SR, SA, and NS by supervised multivariate analysis using partial least squares discriminant analysis (PLS-DA) to determine qualitatively the changes in dermal collagen. These groups are further analyzed for the extent of hydration of dermal collagen by studying the changes in the water content bound to it. PLS-DA score plot showed good separation of the confocal Raman spectra of dermis region into SR, SA, and NS data groups. Further analysis using loading plot and S-plot indicated the participation of various components of dermal collagen in the separation of these groups. Bound water content analysis showed that the extent of hydration of collagen is more in SD when compared to NS. Based on the results obtained, this study confirms the active involvement of dermal collagen in the formation of SD. It also emphasizes the need to study quantitatively the role of these various biochemical changes in the dermal collagen responsible for the variance between SR, SA, and NS.

Dermal contact is the main route of exposure for most cosmetics; however, inhalation exposure could be significant for some formulations (e.g., aerosols, powders). Current cosmetic regulations do not require specific tests addressing respiratory irritation and sensitisation, and despite the prohibition of animal testing for cosmetics, no alternative methods have been validated to assess these endpoints to date. Inhalation hazard is mainly determined based on existing human and animal evidence, read-across, and extrapolation of data from different target organs or tissues, such as the skin. However, because of mechanistic differences, effects on the skin cannot predict effects on the respiratory tract, which indicates a substantial need for the development of new approach methodologies addressing respiratory endpoints for inhalable chemicals in general. Cosmetics might present a particularly significant need for risk assessments of inhalation exposure to provide a more accurate toxicological evaluation and ensure consumer safety. This review describes the differences in the mechanisms of irritation and sensitisation between the skin and the respiratory tract, the progress that has already been made, and what still needs to be done to fill the gap in the inhalation risk assessment of cosmetic ingredients.

Menopause is a stage in a woman's life characterized by twelve months of amenorrhoea. This transition happens due to changes in ovarian follicular activity, leading to endocrine, biological and clinical modifications. The main hormones related to these changes and symptoms are oestradiol, LH, FSH, AMH, Inhibin B and GnRH. It is important to point out that the skin is very affected by all these hormone changes, leading to a decrease in collagen content, water content, elasticity, thickness and impacting on all skin layers quality. Aiming to help women go through this period of their lifetimes with a better quality of life, cosmetic and pharmaceutical industries have studied formulations to improve skin quality. In order to study the safety and efficacy of these products, in vitro methods have been developed in order to mimic menopause and aged skin. In addition to that, many clinical methodologies for skin features assessment have also been improved and applied to evaluate the efficacy of treatments or compounds for menopause. Studying and improving skin models and skin evaluation methodologies may help in the identification of therapeutic targets, treatments, drugs and cosmetics along with new insights for future research in the dermatology field.

Background Striae distensae, commonly known as stretch marks, are cutaneous lesions that accompany the hormonal upheavals of the major stages of life: puberty and pregnancy. Stretch marks occur in 90% of women, and they appear as red or purple lines that slowly fade to pale lines on the skin. There have been few studies regarding stretch mark origins, and new preventive and corrective treatments are needed. Aims The aim of this work was to understand the primary genes and proteins involved in the regulation of striae compared to normal skin and to identify the differentially expressed genes and biochemical aspects of SA and SR Importantly, this is the first published study to use a molecular high-throughput approach combined with in vivo evaluation. Methods In this study, we analyzed the molecular differences between skin with and without stretch marks (rubra [SR] and alba [SA]) of female volunteers using DNA microarray (Whole Human Genome Microarray Kit, 4×44 K, Agilent Technologies) analyses of cutaneous biopsies (2 mm) and in vivo confocal Raman spectroscopy of selected buttock regions, a technique recently introduced as a noninvasive skin evaluation method. Results We identified gene expression alterations related to ECM, cellular homeostasis, and hormones such as secretoglobulins. Spectral analyses of collagen, fibrillin, and glycosaminoglycans were conducted by Raman spectroscopy at different skin depths. The main differences observed when comparing skin with and without stretch marks were at depths between 75 and 95 μm, corresponding to the dermal-epidermal junction and dermis regions and showing differences between normal skin and stretched skin regarding collagen, collagen hydration, and elastin fibers. Conclusion The results obtained by RNA and protein analyses are complementary and show that significant changes occur in the skin affected by stretch marks. These results suggest new strategies and opportunities to treat this skin disorder and for the development of new and eficiente cosmetic products.

Brazil is one of the largest cosmetic markets and represents great opportunities for several beauty niches, including children’s products. Regarding safety assessment and considering the particular needs of the target market, children’s products must be specifically formulated and require special attention to avoid inappropriate use and adverse reactions. Because animal tests are no longer accepted for cosmetic evaluation in Europe, the major challenge in this field is to ensure reliable products using alternative methods and other available data such as those found in the literature. The objective of this study was to define an integrated theoretical and technical rationale for the suitable development of children’s makeup products (lipstick, gloss, blush, and nail polish). Without applying animal methods, formulation safety analyses, toxicological in vitro tests (cytotoxicity, phototoxicity, and skin irritation), and clinical trials were considered. First, a systematic study was performed for selection of the intended ingredients that could be used in each formulation. In vitro methods were applied for the evaluation of cytotoxicity, phototoxicity (following the internationally adopted and validated Organization for Economic Cooperation and Development [OECD] guidance document [GD] OECD GD 129 and test guidelines [TG] OECD TG 432, respectively), and acute skin irritation (using a reconstituted human skin model based on OECD TG 439). Complimentary clinical trials were conducted on adults and children, under pediatrician supervision, for the assessment of skin irritability, sensibility, photoallergy, phototoxicity, and tolerability in real usage conditions. The theoretical components of the rationale for the evaluation of children’s products were based on the following: (1) simple formulations with fewer ingredients in comparison to products for adults; (2) raw materials properly analyzed according to their chemical structures, levels of exposure, and toxicological profiles, including available literature; and (3) fragrances within International Fragrance Association (IFRA) recommendations. Concerning in vitro results, none of the children’s products was identified as phototoxic, as skin irritant, or as significantly cytotoxic in the tested concentrations. Clinical trials also showed negative results for all the toxicological endpoints analyzed, considering adult and children’s panels. The safety rationale developed in the present work, using specific formulation criteria and in vitro alternative methods to animal use, was assertive and well correlated to the results of clinical trials. This rationale represents a practical, integrated, and valuable tool for the development of appropriate formulations and the safety assessment of children’s cosmetic products.

The decisive role of the epidermis in maintaining body homeostasis prompted studies to evaluate the changes in epidermal structure and functionality over the lifetime. This development, along with the identification of molecular mechanisms of epidermal signaling, maintenance, and differentiation, points to a need for new therapeutic alternatives to treat and prevent skin aging. In addition to recovering age- and sun-compromised functions, proper treatment of the epidermis has important esthetic implications. This study reviews active ingredients capable of counteracting symptoms of epidermal aging, organized according to the regulation of specific age-affected epidermal functions: (1) several compounds, other than retinoids and derivatives, act on the proliferation and differentiation of keratinocytes, supporting the protective barrier against mechanical and chemical insults; (2) natural lipidic compounds, as well as glycerol and urea, are described as agents for maintaining water-ion balance; (3) regulation of immunological pathogen defense can be reinforced by natural extracts and compounds, such as resveratrol; and (4) antioxidant exogenous sources enriched with flavonoids and vitamin C, for example, improve solar radiation protection and epidermal antioxidant activity. The main objective is to provide a functional classification of active ingredients as regulatory elements of epidermal homeostasis, with potential cosmetic and/or dermatological applications.

Annona crassiflora (araticum), Eugenia dysenterica (cagaita), and Caryocar brasiliense (pequi) are tropical fruits of the second biggest Brazilian biome: the cerrado. Nowadays, the cerrado faces two different realities: 1) the great possibility of food production since it is considered as the biggest storehouse of the world; and 2) the rich biodiversity that has been newly discovered and known. Previous studies showed that certain cerrado fruits demonstrate high content of total phenols and excellent antioxidant activity in in vitro models. Moreover, using fingerprinting analysis, important bioactive molecules were identified as probably responsible for their antioxidant activity. In this study, the cytotoxicity and phototocixity of ethanolic extracts from cerrado fruits were evaluated using the in vitro Neutral Red Uptake (NRU). Regarding cytotoxicity, the extracts of araticum peel and cagaita seed did not shown any cytotoxic potential up to 300 µg.mL-1. Ethanolic extracts of araticum seed and pequi peel presented low cytotoxic potential and, according to linear regressions, the estimated LD50 were de 831.6 and 2840.7 mg.kg-1, respectively. In the evaluated conditions, only the araticum peel extract presented a phototoxic potential. This is the first attempt to screen the toxicity of cerrado fruits with high antioxidant activity.Annona crassiflora (araticum), Eugenia dysenterica (cagaita) e Caryocar brasiliense (pequi) são frutas do segundo maior bioma brasileiro: o cerrado. Atualmente, o cerrado enfrenta duas realidades diferentes: 1) a grande possibilidade de produção de alimentos, sendo considerado o maior celeiro do mundo; e 2) a riquíssima biodiversidade recentemente descoberta e conhecida. Estudos prévios demonstraram que algumas frutas do cerrado possuem alto conteúdo fenólico e excelente atividade antioxidante em modelos in vitro. Adicionalmente, por meio de análises de fingerprinting, importantes moléculas bioativas foram identificadas como prováveis responsáveis pela atividade antioxidante. Neste estudo, foram avaliadas a citotoxicidade e a fototoxicidade dos extratos etanólicos de frutas do cerrado usando o método in vitro de Neutral Red Uptake (NRU). Em relação à citotoxicidade, os extratos de casca de araticum e semente de cagaita não apresentaram potencial citotóxico até a concentração de 300 µg.mL-1. Extratos etanólicos de semente de araticum e casca de pequi apresentaram baixo potencial citotóxico e por meio de regressões lineares, as LD50 estimadas foram de 831,6 e 2840,7 mg.kg-1, respectivamente. Nas condições avaliadas, somente o extrato de casca de araticum apresentou potencial fototóxico. Esse estudo representa a primeira abordagem para screening de toxicidade de frutos do cerrado com alto poder antioxidante.

Citrus tristeza virus (CTV) is one of the most important citrus pathogen, and among Brazilian CTV strains, the genotype Capão Bonito (CB) is the most harmful. Therefore, the coat protein (CP) gene were cloned and expressed as recombinant protein and used to develop four specific monoclonal antibodies (MAbs). Our previously data had showed these MAbs could recognize different strains of CTV and the present goal is to identify the epitopes of the recombinant CP by ELISA screening of overlapping recombinant peptides and to determine the binding specificity of CTV isolates in light of their antigenic domains onto CB strains. Three MAbs, 30.G.02, 37.G.11 and 39.07 recognized linear and no identical epitopes, but the fourth MAb, IC.04-12, probably had a conformational epitope, since it could not be identified by ELISA screening. Our previous data revealed MAb IC.04-12 do not recognize CP under denaturing conditions, but can identify weak CTV strains in ELISA involving crop samples. MAb 30.G.02 recognized an extremely conserved sequence and can be classified as "universal" antibody, and, interestingly, the epitope turned out by MAb 39.07 corresponded to severe CTV isolates. So, these MAbs can be applied in a differential screening by ELISA.

Bacterial dental plaque is considered to be the main cause of periodontal diseases, but progression of the disease is also related to the host inflammatory response. The earliest affected tissue is the gingiva, but the specific mechanisms involved in the onset of this condition remain unclear. Frequently, collagen degradation is pointed as the main marker of periodontal disease progression, but the organization of the fibers in the gingival tissue is still unknown. The aim of the present study was to investigate the gingival extracellular matrix in a model of ligature-induced periodontal disease. Analysis of the microbiota indicated a progressive increase in the ratio of Gram-negative/Gram-positive microorganisms. There was no difference in the organization of reticulin fibers next to the epithelial basement membrane, whereas the arrangement of collagen fibers in the gingival connective tissue was significantly affected. Animals with inflammation presented a reduction of 35% in the total area occupied by collagen fibers. However, these fibers were thicker and more densely packed. These alterations involve type I, type III and type VI collagens as determined by immunohistochemistry. The results demonstrated the occurrence of marked reorganization of the gingival extracellular matrix in response to the inflammatory process, indicating a new paradigm in the periodontal disease progression: collagen degradation and fibers thickening, simultaneously.

Periodontal disease constitutes the most frequent chronic diseases in human dentition. Bacterial plaque is the main etiologic agent, although it is the host immune response that causes periodontal tissue destruction. Diabetes is considered an important risk factor, not only for the onset but also for progression of the disease. The aim of this study was to analyze structural changes in the rat gingival epithelium and connective tissue in response to the experimental periodontal disease induced by the ligature technique, under the influence of diabetes. The results showed that experimental periodontal disease is characterized by marked inflammation, affecting both the epithelial and connective tissues, causing degeneration of the dermal papilla, increase in the number of inflammatory cells, destruction of reticulin fibers, and accumulation of dense collagen fibers (fibrosis). These changes were worsened by diabetes, apparently by hampering the inflammatory response and affecting tissue repair of the affected tissues.

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. FUNDAMENTOS: A soma de fatores genéticos e ambientais afeta a aparência e a funcionalidade da pele ao longo do envelhecimento. O conhecimento a respeito das mudanças moleculares durante o envelhecimento fornece biomarcadores e possíveis alvos para intervenções terapêuticas. O ácido retinoico em diferentes formulações surgiu como uma alternativa para prevenir e reparar os danos da pele associados ao envelhecimento. OBJETIVOS: Avaliar comparativamente os efeitos de diferentes formulações contendo retinoides na expressão de genes associados a processos biológicos que são alterados com o envelhecimento da pele. MÉTODOS: Peles ex vivo foram topicamente tratadas com diferentes retinoides, micro e nanoencapsulados. A modulação dos processos biológicos associados ao envelhecimento da pele foi medida por PCR quantitativa, precedida de transcrição reversa (RT-qPCR). RESULTADOS: A formulação contendo uma mistura de princípios ativos incorporados em uma tripla nanoemulsão e retinol microencapsulado apresentou os melhores resultados de modulação de genes relacionados a processos biológicos que são normalmente alterados durante o envelhecimento da pele. CONCLUSÃO: Essa associação demonstrou uma maior eficácia terapêutica quando comparada ao uso isolado de tretinoína ou retinol microencapsulado.

Annona crassiflora (araticum), Eugenia dysenterica (cagaita), and Caryocar brasiliense (pequi) are tropical fruits of the second biggest Brazilian biome: the cerrado. Nowadays, the cerrado faces two different realities: 1) the great possibility of food production since it is considered as the biggest storehouse of the world; and 2) the rich biodiversity that has been newly discovered and known. Previous studies showed that certain cerrado fruits demonstrate high content of total phenols and excellent antioxidant activity in in vitro models. Moreover, using fingerprinting analysis, important bioactive molecules were identified as probably responsible for their antioxidant activity. In this study, the cytotoxicity and phototocixity of ethanolic extracts from cerrado fruits were evaluated using the in vitro Neutral Red Uptake (NRU). Regarding cytotoxicity, the extracts of araticum peel and cagaita seed did not shown any cytotoxic potential up to 300 µg.mL-1. Ethanolic extracts of araticum seed and pequi peel presented low cytotoxic potential and, according to linear regressions, the estimated LD50 were de 831.6 and 2840.7 mg.kg-1, respectively. In the evaluated conditions, only the araticum peel extract presented a phototoxic potential. This is the first attempt to screen the toxicity of cerrado fruits with high antioxidant activity. Annona crassiflora (araticum), Eugenia dysenterica (cagaita) e Caryocar brasiliense (pequi) são frutas do segundo maior bioma brasileiro: o cerrado. Atualmente, o cerrado enfrenta duas realidades diferentes: 1) a grande possibilidade de produção de alimentos, sendo considerado o maior celeiro do mundo; e 2) a riquíssima biodiversidade recentemente descoberta e conhecida. Estudos prévios demonstraram que algumas frutas do cerrado possuem alto conteúdo fenólico e excelente atividade antioxidante em modelos in vitro. Adicionalmente, por meio de análises de fingerprinting, importantes moléculas bioativas foram identificadas como prováveis responsáveis pela atividade antioxidante. Neste estudo, foram avaliadas a citotoxicidade e a fototoxicidade dos extratos etanólicos de frutas do cerrado usando o método in vitro de Neutral Red Uptake (NRU). Em relação à citotoxicidade, os extratos de casca de araticum e semente de cagaita não apresentaram potencial citotóxico até a concentração de 300 µg.mL-1. Extratos etanólicos de semente de araticum e casca de pequi apresentaram baixo potencial citotóxico e por meio de regressões lineares, as LD50 estimadas foram de 831,6 e 2840,7 mg.kg-1, respectivamente. Nas condições avaliadas, somente o extrato de casca de araticum apresentou potencial fototóxico. Esse estudo representa a primeira abordagem para screening de toxicidade de frutos do cerrado com alto poder antioxidante.

In periodontal disease, extensive disorganization of the extracellular matrix promotes the loss of adhesion between the teeth and periodontium. A previous study suggested a reduction in the area occupied by collagen in the gingiva, during the first week of periodontal disease induction, however, the remaining fibers were more compact and thicker. Therefore, it was decided to investigate which of the MMP-2, -9, -14 and RECK, an MMP inhibitor, were involved in these modifications taking place in early gingivitis induced by ligature. The results of gene expression analysis indicated no changes for RECK. MMP-14 showed a reduction at 7 days of inflammation, and there was an immediate increase in MMP-2 gene expression and enzymatic activity, apparently by the stimulation of resident cells such as fibroblasts. A peak of MMP-9 expression 5 days after ligature followed after the peak of enzymatic activity found two days earlier. This pattern was consistent with the kinetics of macrophage and neutrophil recruitment. Immunohistochemistry suggested that MMP-9 was produced by both resident and inflammatory cells. Based on this evidence, it is suggested that extracellular matrix remodeling is related to MMP-2 and -9 production and activation. This allowed us to conclude that the host inflammatory response represents a significant factor for the advance of periodontal diseases.

Background and Objective: Periodontal disease corresponds to a group of lesions that affect the tooth-supporting tissues present in the dental follicle. Although bacterial plaque is important, the immune response also contributes to the destruction of periodontal tissues. Diabetes mellitus is closely associated with the development, progression and severity of periodontal disease because it not only affects extracellular matrix organization but also the tissue response to inflammation. The objective of the present investigation was to study the influence of diabetes on experimental periodontal disease by evaluating the degradation of extracellular matrix through the analysis of matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity, using immunofluorescence, zymography and real-time reverse transcription-polymerase chain reaction. Material and Methods: Wistar rats were divided into normal and diabetic groups and evaluated 0, 15 and 30 d after the induction of periodontal disease by ligature. Results: MMP-2 and -9 were detected in epithelial cells, in the blood vessel endothelium and in connective tissue cells. The same profile of enzymatic expression of MMP-2 and -9 was observed in normal and diabetic animals, with a peak in activity at day 15 of inflammation. However, in diabetic animals, MMP-2 gelatinolytic activity was reduced after the inflammatory stimulus, whereas that of MMP-9 was increased. MMP-2 gene expression decreased with inflammation in both normal groups and groups with diabetes. In contrast, MMP-9 expression increased in normal animals and decreased in diabetic animals after inflammation. Conclusion: The results suggest the involvement of MMP-2 and -9 in the dynamics of periodontal disease and that variation in their expression levels results in differences in tissue organization and wound healing in normal and diabetic animals.