374 results on '"A. Trovato-Salinaro"'
Search Results
2. Hormetic Nutrition and Redox Regulation in Gut–Brain Axis Disorders
- Author
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Maria Scuto, Francesco Rampulla, Giuseppe Maria Reali, Sestina Maria Spanò, Angela Trovato Salinaro, and Vittorio Calabrese
- Subjects
Gut–brain axis ,inflammation ,Nrf2 pathway ,hormesis ,probiotics ,polyphenols ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience and overall human health have received much attention. Recently, the gut–brain axis has attracted prominent interest for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy with probiotics have shown to improve gut bioavailability and blood–brain barrier (BBB) permeability, thus inhibiting the oxidative stress, metabolic dysfunction and inflammation linked to gut dysbiosis and ultimately the onset and progression of central nervous system (CNS) disorders. In accordance with hormesis, polyphenols display biphasic dose–response effects by activating at a low dose the Nrf2 pathway resulting in the upregulation of antioxidant vitagenes, as in the case of heme oxygenase-1 upregulated by hidrox® or curcumin and sirtuin-1 activated by resveratrol to inhibit reactive oxygen species (ROS) overproduction, microbiota dysfunction and neurotoxic damage. Importantly, modulation of the composition and function of the gut microbiota through polyphenols and/or probiotics enhances the abundance of beneficial bacteria and can prevent and treat Alzheimer’s disease and other neurological disorders. Interestingly, dysregulation of the Nrf2 pathway in the gut and the brain can exacerbate selective susceptibility under neuroinflammatory conditions to CNS disorders due to the high vulnerability of vagal sensory neurons to oxidative stress. Herein, we aimed to discuss hormetic nutrients, including polyphenols and/or probiotics, targeting the Nrf2 pathway and vitagenes for the development of promising neuroprotective and therapeutic strategies to suppress oxidative stress, inflammation and microbiota deregulation, and consequently improve cognitive performance and brain health. In this review, we also explore interactions of the gut–brain axis based on sophisticated and cutting-edge technologies for novel anti-neuroinflammatory approaches and personalized nutritional therapies.
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- 2024
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3. Changes in the Biomarkers of Oxidative/Nitrosative Stress and Endothelial Dysfunction Are Associated with Cardiovascular Risk in Periodontitis Patients
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Nadia Ferlazzo, Monica Currò, Gaetano Isola, Silvia Maggio, Maria Paola Bertuccio, Angela Trovato-Salinaro, Giovanni Matarese, Angela Alibrandi, Daniela Caccamo, and Riccardo Ientile
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3-nitrotyrosine (NT) ,asymmetric dimethylarginine (ADMA) ,cardiovascular disease ,coenzyme Q10 (CoQ10) ,inflammasome ,peripheral blood mononuclear cells (PBMC) ,Biology (General) ,QH301-705.5 - Abstract
Patients with cardiovascular disease (CVD) and periodontitis (PT) show shared risk factors as result of the altered molecular mechanisms associated with pathological conditions. The aim of our study was to evaluate if the plasma biomarkers associated with endothelial dysfunction may also be related to alterations in the inflammatory status in peripheral blood mononuclear cells (PBMC). Patients with PT, coronary heart disease (CHD), or both diseases as well as controls were enrolled. Plasma levels of coenzyme Q10 (CoQ10), 3-nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) were assessed using HPLC. mRNA levels of caspase-1 (CASP1), NLR family pyrin domain containing 3 (NLRP3), and tumor necrosis factor-α (TNF-α) in PBMC from the recruited subjects were quantified using real-time PCR. Patients with PT + CHD showed lower CoQ10 plasma levels and increased concentrations of NT in comparison to healthy subjects. ADMA levels were higher in CHD and PT + CHD patients compared to controls. Transcript levels of CASP1, NLRP3, and TNF-α were up-regulated in PBMC from all patient groups when compared to healthy subjects. Our results suggest a possible causal link between oxidative stress, high levels of NT and ADMA, and inflammasome activation, which may be involved in the endothelial inflammatory dysfunction leading to the pathogenesis and progression of CHD in PT patients.
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- 2021
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4. Pericytes of Stria Vascularis Are Targets of Cisplatin-Induced Ototoxicity: New Insights into the Molecular Mechanisms Involved in Blood-Labyrinth Barrier Breakdown
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Carmelina Daniela Anfuso, Alessia Cosentino, Aleksandra Agafonova, Agata Zappalà, Giovanni Giurdanella, Angela Trovato Salinaro, Vittorio Calabrese, and Gabriella Lupo
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cochlear pericytes ,stria vascularis ,cisplatin ,phospholipase A2 ,inflammation ,VEGF ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The stria vascularis (SV) contributes to cochlear homeostasis and consists of three layers, one of which contains the blood-labyrinthic barrier (BLB), with a large number of bovine cochlear pericytes (BCPs). Cisplatin is a chemotherapeutic drug that can damage the SV and cause hearing loss. In this study, cell viability, proliferation rate, cytotoxicity and reactive oxygen species production were evaluated. The protein content of phospho-extracellular signal-regulated kinases (ERK) 1/2, total ERK 1/2, phospho-cytosolic phospholipase A2 (cPLA2), total cPLA2 and cyclooxygenase 2 (COX-2) and the release of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) from BCPs were analyzed. Finally, the protective effect of platelet-derived growth factor (PDGF-BB) on BCPs treated with cisplatin was investigated. Cisplatin reduced viability and proliferation, activated ERK 1/2, cPLA2 and COX-2 expression and increased PGE2 and VEGF release; these effects were reversed by Dexamethasone. The presence of PDGF-BB during the treatment with cisplatin significantly increased the proliferation rate. No studies on cell regeneration in ear tissue evaluated the effect of the PDGF/Dex combination. The aim of this study was to investigate the effects of cisplatin on cochlear pericytes and propose new otoprotective agents aimed at preventing the reduction of their vitality and thus maintaining the BLB structure.
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- 2022
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5. Anserine and Carnosine Induce HSP70-Dependent H2S Formation in Endothelial Cells and Murine Kidney
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Charlotte Wetzel, Tilman Pfeffer, Ruben Bulkescher, Johanna Zemva, Sergio Modafferi, Alessandra Polimeni, Angela Trovato Salinaro, Vittorio Calabrese, Claus Peter Schmitt, and Verena Peters
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anserine ,carnosine ,diabetic nephropathy ,hydrogen sulfide ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Anserine and carnosine have nephroprotective actions; hydrogen sulfide (H2S) protects from ischemic tissue damage, and the underlying mechanisms are debated. In view of their common interaction with HSP70, we studied possible interactions of both dipeptides with H2S. H2S formation was measured in human proximal tubular epithelial cells (HK-2); three endothelial cell lines (HUVEC, HUAEC, MCEC); and in renal murine tissue of wild-type (WT), carnosinase-1 knockout (Cndp1-KO) and Hsp70-KO mice. Diabetes was induced by streptozocin. Incubation with carnosine increased H2S synthesis capacity in tubular cells, as well as with anserine in all three endothelial cell lines. H2S dose-dependently reduced anserine/carnosine degradation rate by serum and recombinant carnosinase-1 (CN1). Endothelial Hsp70-KO reduced H2S formation and abolished the stimulation by anserine and could be restored by Hsp70 transfection. In female Hsp70-KO mice, kidney H2S formation was halved. In Cndp1-KO mice, kidney anserine concentrations were several-fold and sex-specifically increased. Kidney H2S formation capacity was increased 2–3-fold in female mice and correlated with anserine and carnosine concentrations. In diabetic Cndp1-KO mice, renal anserine and carnosine concentrations as well as H2S formation capacity were markedly reduced compared to non-diabetic Cndp1-KO littermates. Anserine and carnosine induce H2S formation in a cell-type and Hsp70-specific manner within a positive feedback loop with CN1.
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- 2022
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6. Hormetic Nutrition and Redox Regulation in Gut–Brain Axis Disorders.
- Author
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Scuto, Maria, Rampulla, Francesco, Reali, Giuseppe Maria, Spanò, Sestina Maria, Trovato Salinaro, Angela, and Calabrese, Vittorio
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PROBIOTICS ,ALZHEIMER'S disease ,NUTRITION ,GUT microbiome ,CENTRAL nervous system ,REACTIVE oxygen species - Abstract
The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience and overall human health have received much attention. Recently, the gut–brain axis has attracted prominent interest for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy with probiotics have shown to improve gut bioavailability and blood–brain barrier (BBB) permeability, thus inhibiting the oxidative stress, metabolic dysfunction and inflammation linked to gut dysbiosis and ultimately the onset and progression of central nervous system (CNS) disorders. In accordance with hormesis, polyphenols display biphasic dose–response effects by activating at a low dose the Nrf2 pathway resulting in the upregulation of antioxidant vitagenes, as in the case of heme oxygenase-1 upregulated by hidrox
® or curcumin and sirtuin-1 activated by resveratrol to inhibit reactive oxygen species (ROS) overproduction, microbiota dysfunction and neurotoxic damage. Importantly, modulation of the composition and function of the gut microbiota through polyphenols and/or probiotics enhances the abundance of beneficial bacteria and can prevent and treat Alzheimer's disease and other neurological disorders. Interestingly, dysregulation of the Nrf2 pathway in the gut and the brain can exacerbate selective susceptibility under neuroinflammatory conditions to CNS disorders due to the high vulnerability of vagal sensory neurons to oxidative stress. Herein, we aimed to discuss hormetic nutrients, including polyphenols and/or probiotics, targeting the Nrf2 pathway and vitagenes for the development of promising neuroprotective and therapeutic strategies to suppress oxidative stress, inflammation and microbiota deregulation, and consequently improve cognitive performance and brain health. In this review, we also explore interactions of the gut–brain axis based on sophisticated and cutting-edge technologies for novel anti-neuroinflammatory approaches and personalized nutritional therapies. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
7. Blood–Labyrinth Barrier in Health and Diseases: Effect of Hormetic Nutrients.
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Cosentino, Alessia, Agafonova, Aleksandra, Modafferi, Sergio, Trovato Salinaro, Angela, Scuto, Maria, Maiolino, Luigi, Fritsch, Tilman, Calabrese, Edward J., Lupo, Gabriella, Anfuso, Carmelina Daniela, and Calabrese, Vittorio
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- 2024
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8. S-Acetyl-Glutathione Attenuates Carbon Tetrachloride-Induced Liver Injury by Modulating Oxidative Imbalance and Inflammation
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Rosanna Di Paola, Sergio Modafferi, Rosalba Siracusa, Marika Cordaro, Ramona D’Amico, Maria Laura Ontario, Livia Interdonato, Angela Trovato Salinaro, Roberta Fusco, Daniela Impellizzeri, Vittorio Calabrese, and Salvatore Cuzzocrea
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liver fibrosis ,antioxidant ,inflammation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Liver fibrosis, depending on the stage of the disease, could lead to organ dysfunction and cirrhosis, and no effective treatment is actually available. Emergent proof supports a link between oxidative stress, liver fibrogenesis and mitochondrial dysfunction as molecular bases of the pathology. A valid approach to protect against the disease would be to replenish the endogenous antioxidants; thus, we investigated the protective mechanisms of the S-acetyl-glutathione (SAG), a glutathione (GSH) prodrug. Preliminary in vitro analyses were conducted on primary hepatic cells. SAG pre-treatment significantly protected against cytotoxicity induced by CCl4. Additionally, CCl4 induced a marked increase in AST and ALT levels, whereas SAG significantly reduced these levels, reaching values found in the control group. For the in vivo analyses, mice were administered twice a week with eight consecutive intraperitoneal injections of 1 mL/kg CCl4 (diluted at 1:10 in olive oil) to induce oxidative imbalance and liver inflammation. SAG (30 mg/kg) was administered orally for 8 weeks. SAG significantly restored SOD activity, GSH levels and GPx activity, while it strongly reduced GSSG levels, lipid peroxidation and H2O2 and ROS levels in the liver. Additionally, CCl4 induced a decrease in anti-oxidants, including Nrf2, HO-1 and NQO-1, which were restored by treatment with SAG. The increased oxidative stress characteristic on liver disfunction causes the impairment of mitophagy and accumulation of dysfunctional and damaged mitochondria. Our results showed the protective effect of SAG administration in restoring mitophagy, as shown by the increased PINK1 and Parkin expressions in livers exposed to CCl4 intoxication. Thus, the SAG administration showed anti-inflammatory effects decreasing pro-inflammatory cytokines TNF-α, IL-6, MCP-1 and IL-1β in both serum and liver, and suppressing the TLR4/NFkB pathway. SAG attenuated reduced fibrosis, collagen deposition, hepatocellular damage and organ dysfunction. In conclusion, our results suggest that SAG administration protects the liver from CCl4 intoxication by restoring the oxidative balance, ameliorating the impairment of mitophagy and leading to reduced inflammation.
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- 2022
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9. Coriolus Versicolor Downregulates TLR4/NF-κB Signaling Cascade in Dinitrobenzenesulfonic Acid-Treated Mice: A Possible Mechanism for the Anti-Colitis Effect
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Daniela Impellizzeri, Roberta Fusco, Tiziana Genovese, Marika Cordaro, Ramona D’Amico, Angela Trovato Salinaro, Maria Laura Ontario, Sergio Modafferi, Salvatore Cuzzocrea, Rosanna Di Paola, Vittorio Calabrese, and Rosalba Siracusa
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inflammatory bowel diseases ,inflammation ,oxidative stress ,natural compounds ,TLR4 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Inflammatory bowel diseases (IBDs) are disorders characterized by chronic inflammation of the intestinal tract. The focus of the present study was to examine the effect of the fungus Coriolus versicolor (CV), underlining its correlation with Toll-like receptors 4 (TLR4) and nuclear factor erythroid 2-related factor 2 (Nrf2); we aim to evaluate its anti-inflammatory and antioxidant effect in mice exposed to experimental colitis. The model was induced in mice by colon instillation of dinitrobenzenesulfonic acid (DNBS), CV was administered orally (200 mg per kg) daily for 4 days. On day 4, the animals were killed, and the tissues collected for histological, biochemical, and molecular analyses. Four days after DNBS administration, CC motif chemokine ligand 2 (CCL2), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) production increased in association with damage to the colon. Neutrophil infiltration, as assessed by myeloperoxidase (MPO) activity, in the mucosa was associated with overexpression of P-selectin and intercellular adhesion molecule 1 (ICAM1). Immunohistochemistry for nitrotyrosine and poly-(ADP-Ribose)-polymerase (PARP) showed evident stain in the inflamed colon. Treatment with CV significantly reduced the appearance of colon changes and weight loss. These effects were associated with a remarkable ability of CV to reduce the expression of TLR4 and modulate the pathway of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). This improved the colon architecture, reduced MPO activity, the release of proinflammatory cytokines, the presence of nitrotyrosine, and the hyperactivation of PARP, as well as the up-regulation of P-selectin and ICAM1. Furthermore, we studied the action of CV on the Nrf2/HO-1 pathway, which is important for maintaining redox balance, demonstrating that CV by significantly increasing both enzymes is able to counteract the oxidative stress induced by DNBS. Taken together, our results clearly show that this natural compound can be considered as a possible dietary supplement against colitis.
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- 2022
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10. Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: modulation by nutritional mushrooms
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Angela Trovato Salinaro, Manuela Pennisi, Rosanna Di Paola, Maria Scuto, Rosalia Crupi, Maria Teresa Cambria, Maria Laura Ontario, Mario Tomasello, Maurizio Uva, Luigi Maiolino, Edward J. Calabrese, Salvatore Cuzzocrea, and Vittorio Calabrese
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Oxidative stress ,Neurodegenerative disorders ,Neurohormesis ,Mushrooms ,Immunologic diseases. Allergy ,RC581-607 ,Geriatrics ,RC952-954.6 - Abstract
Abstract Human life develops and expands not only in time and space, but also in the retrograde permanent recollection and interweaving of memories. Therefore, individual human identity depends fully on a proper access to the autobiographical memory. Such access is hindered or lost under pathological conditions such as Alzheimer’s disease, including recently associated oxidant pathologies, such as ocular neural degeneration occurring in glaucoma or neurosensorial degeneration occurring in Menière’s disease. Oxidative stress and altered antioxidant systems have been suggested to play a role in the aetiology of major neurodegenerative disorders, and altered expression of genes sensing oxidative stress, as well as decreased cellular stress response mechanisms could synergistically contribute to the course of these oxidant disorders. Thus, the theory that low levels of stress can produce protective responses against the pathogenic processes is a frontier area of neurobiological research focal to understanding and developing therapeutic approaches to neurodegenerative disorders. Herein, we discuss cellular mechanisms underlying AD neuroinflammatory pathogenesis that are contributory to Alzheimer’s disease. We describe endogenous cellular defence mechanism modulation and neurohormesis as a potentially innovative approach to therapeutics for AD and other neurodegenerative conditions that are associated with mitochondrial dysfunction and neuroinflammation. Particularly, we consider the emerging role of the inflammasome as an important component of the neuroprotective network, as well as the importance of Coriolus and Hericium nutritional mushrooms in redox stress responsive mechanisms and neuroprotection.
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- 2018
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11. Anti-Candidal Activity of the Parasitic Plant Orobanche crenata Forssk
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Floriana D’Angeli, Fiorella Guadagni, Carlo Genovese, Daria Nicolosi, Angela Trovato Salinaro, Mariarita Spampinato, Giuliana Mannino, Debora Lo Furno, Giulio Petronio Petronio, Simone Ronsisvalle, Federica Sipala, Luca Falzone, and Vittorio Calabrese
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Orobanche crenata ,parasitic plant ,Candida spp. ,phenotypic switching ,biofilm ,adhesion ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Candida albicans (C. albicans) and Candida glabrata (C. glabrata) are part of the human microbiome. However, they possess numerous virulence factors, which confer them the ability to cause both local and systemic infections. Candidiasis can involve multiple organs, including the eye. In the present study, we investigated the anti-candidal activity and the re-epithelizing effect of Orobanche crenata leaf extract (OCLE). By the microdilution method, we demonstrated an inhibitory effect of OCLE on both C. albicans and C. glabrata growth. By crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of OCLE to inhibit the biofilm formation and the viability of yeast cells, respectively. By germ tube and adhesion assays, we proved the capacity of OCLE to affect the morphological transition of C. albicans and the adhesion of both pathogens to human retinal pigment epithelial cells (ARPE-19), respectively. Besides, by MTT and wound healing assay, we evaluated the cytotoxic and re-epithelizing effects of OCLE on ARPE-19. Finally, the Folin–Ciocalteu and the ultra-performance liquid chromatography-tandem mass spectrometry revealed a high content of phenols and the presence of several bioactive molecules in the extract. Our results highlighted new properties of O. crenata, useful in the control of Candida infections.
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- 2021
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12. Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®
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Ramona D’Amico, Marika Cordaro, Rosalba Siracusa, Daniela Impellizzeri, Angela Trovato Salinaro, Maria Scuto, Maria Laura Ontario, Roberto Crea, Salvatore Cuzzocrea, Rosanna Di Paola, Roberta Fusco, and Vittorio Calabrese
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fibromyalgia ,pain ,WNT/β-catenin pathway ,Nrf2 pathway ,Biology (General) ,QH301-705.5 - Abstract
Fibromyalgia (FM) is a chronic condition characterized by persistent widespread pain that negatively affects the quality of life of patients. The WNT/β-catenin signaling pathway seems to be involved in central sensitization and different pain states. The objective of this study was to investigate the beneficial effects of a new compound called Hidrox® (HD), containing 40–50% hydroxytyrosol, in counteracting the pain associated with FM. An FM-like model was induced in rats by subcutaneous injections of reserpine (1 mg/kg) for three consecutive days. Later, HD (10 mg/kg) was administered orally to the animals for seven days. Reserpine injections induced WNT/β-catenin pathway activation, release of pro-inflammatory mediators as well as a significant increase in oxidative stress. Daily treatment with HD was able to modulate the WNT/β-catenin and Nrf2 pathways and consequently attenuate the behavioral deficits and microglia activation induced by reserpine injection. These results indicate that nutritional consumption of HD can be considered as a new therapeutic approach for human FM.
- Published
- 2021
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13. Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease
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Marika Cordaro, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D’Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Salvatore Cuzzocrea, Rosanna Di Paola, Roberta Fusco, and Vittorio Calabrese
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inflammasome ,Alzheimer’s disease ,oxidative stress ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and Hericium erinaceus was administered daily by gavage. Before the experiment’s end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. Hericium erinaceus administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, Hericium erinaceus decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that Hericium erinaceus has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress.
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- 2021
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14. Atrazine Inhalation Causes Neuroinflammation, Apoptosis and Accelerating Brain Aging
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Tiziana Genovese, Rosalba Siracusa, Roberta Fusco, Ramona D’Amico, Daniela Impellizzeri, Alessio Filippo Peritore, Rosalia Crupi, Enrico Gugliandolo, Rossana Morabito, Salvatore Cuzzocrea, Angela Trovato Salinaro, Marika Cordaro, and Rosanna Di Paola
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atrazine ,endocrine disruptor ,oxidative stress ,inflammation ,brain alterations ,aging ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Background: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain’s neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. Methods: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. Results: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. Conclusions: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.
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- 2021
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15. Regulation of Inflammatory and Proliferative Pathways by Fotemustine and Dexamethasone in Endometriosis
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Tiziana Genovese, Rosalba Siracusa, Ramona D’Amico, Marika Cordaro, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Angela Trovato Salinaro, Emanuela Raffone, Daniela Impellizzeri, Salvatore Cuzzocrea, Roberta Fusco, and Rosanna Di Paola
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endometriosis ,inflammation ,pathways ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Endometriosis is a common disease. Its pathogenesis still remains uncertain, but it is clear that cell proliferation, apoptosis and chronic inflammation play an important role in its development. This paper aimed to investigate the anti-proliferative and anti-inflammatory effects of a combined therapy with fotemustine and dexamethasone. Endometriosis was induced by intraperitoneal injections of uterine fragments from donor animals to recipient animals. Next, the pathology was allowed to develop for 7 days. On the seventh day, fotemustine was administered once and dexamethasone was administered daily for the next 7 days. On Day 14, the animals were sacrificed, and peritoneal fluids and lesions were explanted. In order to evaluate the gastrointestinal side effects of the drugs, stomachs were harvested as well. The combined therapy of fotemustine and dexamethasone reduced the proinflammatory mediator levels in the peritoneal fluid and reduced the lesions’ area and diameter. In particular, fotemustine and dexamethasone administration reduced the heterogeneous development of endometrial stroma and glands (histological analysis of lesions) and hyperproliferation of endometriotic cells (immunohistochemical analysis of Ki67 and Western blot analysis of PCNA) through the mitogen-activated protein kinase (MAPK) signaling pathway. Combined fotemustine and dexamethasone therapy showed anti-inflammatory effects by inducing the synthesis of anti-inflammatory mediators at the transcriptional and post-transcriptional levels (Western blot analysis of NFκB, COX-2 and PGE2 expression). Fotemustine and dexamethasone administration had anti-apoptotic activity, restoring the impaired mechanism (TUNEL assay and Western blot analysis of Bax and Bcl-2). Moreover, no gastric disfunction was detected (histological analysis of stomachs). Thus, our data showed that the combined therapy of fotemustine and dexamethasone reduced endometriosis-induced inflammation, hyperproliferation and apoptosis resistance.
- Published
- 2021
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16. Hericium erinaceus and Coriolus versicolor Modulate Molecular and Biochemical Changes after Traumatic Brain Injury
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Ramona D’Amico, Angela Trovato Salinaro, Roberta Fusco, Marika Cordaro, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Gianluigi Lo Dico, Salvatore Cuzzocrea, Rosanna Di Paola, Rosalba Siracusa, and Vittorio Calabrese
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brain trauma ,neurodegeneration ,neuroinflammation ,oxidative stress ,mushrooms ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Traumatic brain injury (TBI) is a major health and socioeconomic problem affecting the world. This condition results from the application of external physical force to the brain which leads to transient or permanent structural and functional impairments. TBI has been shown to be a risk factor for neurodegeneration which can lead to Parkinson’s disease (PD) for example. In this study, we wanted to explore the development of PD-related pathology in the context of an experimental model of TBI and the potential ability of Coriolus versicolor and Hericium erinaceus to prevent neurodegenerative processes. Traumatic brain injury was induced in mice by controlled cortical impact. Behavioral tests were performed at various times: the animals were sacrificed 30 days after the impact and the brain was processed for Western blot and immunohistochemical analyzes. After the head injury, a significant decrease in the expression of tyrosine hydroxylase and the dopamine transporter in the substantia nigra was observed, as well as significant behavioral alterations that were instead restored following daily oral treatment with Hericium erinaceus and Coriolus versicolor. Furthermore, a strong increase in neuroinflammation and oxidative stress emerged in the vehicle groups. Treatment with Hericium erinaceus and Coriolus versicolor was able to prevent both the neuroinflammatory and oxidative processes typical of PD. This study suggests that PD-related molecular events may be triggered on TBI and that nutritional fungi such as Hericium erinaceus and Coriolus versicolor may be important in redox stress response mechanisms and neuroprotection, preventing the progression of neurodegenerative diseases such as PD.
- Published
- 2021
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17. Hidrox® and Chronic Cystitis: Biochemical Evaluation of Inflammation, Oxidative Stress, and Pain
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Ramona D’Amico, Angela Trovato Salinaro, Marika Cordaro, Roberta Fusco, Daniela Impellizzeri, Livia Interdonato, Maria Scuto, Maria Laura Ontario, Roberto Crea, Rosalba Siracusa, Salvatore Cuzzocrea, Rosanna Di Paola, and Vittorio Calabrese
- Subjects
chronic disease ,inflammation ,oxidative stress ,pain ,natural compound ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, inflammation, oxidative stress, and pain. The aim of the study was to evaluate the anti-inflammatory and antioxidant effects of an oral administration of Hidrox® (10 mg/kg) in the bladder and spinal cord in a rodent model of IC/BPS. The chronic animal model of cystitis was induced by repeated intraperitoneal injections of cyclophosphamide (CYP) for five consecutive days. Treatment with Hidrox® began on the third day of the CYP injection and continued until the 10th day. CYP administration caused macroscopic and histological bladder changes, inflammatory infiltrates, increased mast cell numbers, oxidative stress, decreased expression of the tight endothelial junction (e.g., zonula occludens-1 (ZO-1) and occludin), and bladder pain. Treatment with Hidrox® was able to improve CYP-induced inflammation and oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. It was also able to reduce bladder pain which was aggravated by the activation of neuroinflammation in the central nervous system. In particular, Hidrox® reduced the brain-derived neurotrophic factor (BDNF), as well as the activation of astrocytes and microglia, consequently reducing mechanical allodynia. These results indicate that nutritional consumption of Hidrox® can be considered as a new therapeutic approach for human cystitis, increasing the conceivable potential of a significant improvement in the quality of life associated with a lowering of symptom intensity in patients with IC/BPS.
- Published
- 2021
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18. Hidrox® and Endometriosis: Biochemical Evaluation of Oxidative Stress and Pain
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Marika Cordaro, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D'Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Livia Interdonato, Roberto Crea, Roberta Fusco, Salvatore Cuzzocrea, Rosanna Di Paola, and Vittorio Calabrese
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endometriosis ,oxidative stress ,pain ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Endometriosis is a gynecological and painful condition affecting women of reproductive age. It is characterized by dysfunctional endometrium-like implants outside of the uterine cavity. The purpose of this study was to evaluate the effects of Hidrox®, an aqueous extract of olive pulp containing hydroxytyrosol, on endometriotic lesions associated with pro-oxidative alterations and pain-like behaviors. Endometriosis was induced by intraperitoneal injection of uterine fragments, and Hidrox® was administered daily. At the end of the 14-day treatment, behavioral alterations were assessed and hippocampal tissues were collected. Laparotomy was performed, and the endometrial implants were harvested for histological and biochemical analysis. Hidrox® treatment reduced endometriotic implant area, diameter and volumes. Vehicle-treated rats showed lesional fibrosis, epithelial–mesenchymal transition and fibroblast–myofibroblast transdifferentiation, angiogenesis and pro-oxidative alterations in the peritoneal cavity. Hidrox® treatment reduced the aniline blue-stained area, α-smooth muscle actin (α-sma) and CD34 positive expressions. Moreover, it reduced mast cell recruitment into the lesions, myeloperoxidase activity and lipid peroxidation and increased superoxide dismutase (SOD) activity and glutathione levels in the endometrial explants. In the peritoneal fluid, Hidrox® treatment reduced interleukin (IL)-1β, IL2, IL6, tumor necrosis factor-α (TNF-α) and vascular endothelial grow factor (VEGF) levels increased by the disease. Hidrox® administration also reduced peripheral and visceral sensibility as shown by the behavioral tests (open field test, hot plate test, elevated plus maze test and acetic-acid-induced abdominal contractions). Animals treated with Hidrox® also showed reduced blood–brain barrier permeability and mast cell infiltration in the hippocampus, as well as astrocyte and microglia activation and brain oxidative status restoring brain-derived neurotrophic factor (BDNF) protein expression and increasing Nuclear factor erythroid 2-related factor 2 (Nfr2) nuclear translocation. In conclusion, Hidrox® displayed potential ameliorative effects on endometriotic implants and related pain-induced behaviors due to its potent antioxidative properties.
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- 2021
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19. Autophagy and Mitophagy Promotion in a Rat Model of Endometriosis
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Rosalba Siracusa, Ramona D’Amico, Daniela Impellizzeri, Marika Cordaro, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Angela Trovato Salinaro, Emanuela Raffone, Tiziana Genovese, Salvatore Cuzzocrea, Roberta Fusco, and Rosanna Di Paola
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autophagy ,mitophagy ,endometriosis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Endometriosis is a gynecological condition affecting patients in reproductive age. The aim of this paper was to assess the effects of the autophagy and mitophagy induction in a rat model of endometriosis. Endometriosis was induced by the injection of uterine fragments, and rapamycin (0. 5 mg/kg) was administered once per week. One week from the induction, rats were sacrificed, and laparotomy was performed to collect the endometriotic implants and to further process them for molecular analysis. Western blot analysis was conducted on explanted lesions to evaluate the autophagy pathway during the pathology. Elevated phospho-serine/threonine kinase (p-AKT) and mammalian target of rapamycin (mTOR) expressions were detected in vehicle-treated rats, while Beclin and microtubule-associated protein 1A/1B-light chain 3 II (LC3II) expressions were low. Additionally, samples collected from vehicle groups indicated low Bnip3, Ambra1, and Parkin expressions, demonstrating impaired autophagy and mitophagy. Rapamycin administration reduced p-AKT and mTOR expressions and increased Beclin and LC3II, Bnip3, Ambra1, and Parkin expressions, activating both mechanisms. We also evaluated the impact of the impaired autophagy and mitophagy pathways on apoptosis and angiogenesis. Rapamycin was administered by activating autophagy and mitophagy, which increased apoptosis (assessed by Western blot analysis of Bcl-2, Bax, and Cleaved-caspase 3) and reduced angiogenesis (assessed by immunohistochemical analysis of vascular endothelial grow factor (VEGF) and CD34) in the lesions. All of these mechanisms activated by the induction of the autophagy and mitophagy pathways led to the reduction in the lesions’ volume, area and diameter.
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- 2021
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20. Hidrox® Counteracts Cyclophosphamide-Induced Male Infertility through NRF2 Pathways in a Mouse Model
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Roberta Fusco, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D’Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Roberto Crea, Marika Cordaro, Salvatore Cuzzocrea, Rosanna Di Paola, and Vittorio Calabrese
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Nrf2 ,oxidative stress ,inflammation ,cyclophosphamide ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Every year, men use cyclophosphamide to treat various cancers and autoimmune diseases. On the one hand, this chemotherapy often has the beneficial effect of regressing the tumor, but on the other hand, it leads to infertility due to excessive oxidative stress and apoptosis in the testes caused by its metabolite, acrolein. Methods: The objective of this study was to evaluate the beneficial power of a new compound called Hidrox®, containing 40–50% hydroxytyrosol, in counteracting the damage related to fertility induced by cyclophosphamide. The study was conducted using a single intraperitoneal injection of cyclophosphamide at a dose of 200 mg/kg b.w, in distilled water at 10 mL/kg b.w. The treatment was administered via the oral administration of Hidrox® at a dose of 50 mg/kg. Results: Our study confirms that the use of cyclophosphamide causes a series of sperm and histological alterations strongly connected with oxidative stress, lipid peroxidation, and apoptosis. Conclusion: Our results demonstrate for the first time that Hidrox® protects testes from CYP-induced alterations by the modulation of physiological antioxidant defenses.
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- 2021
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21. Hidrox® Roles in Neuroprotection: Biochemical Links between Traumatic Brain Injury and Alzheimer’s Disease
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Marika Cordaro, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D’Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Roberto Crea, Salvatore Cuzzocrea, Rosanna Di Paola, Roberta Fusco, and Vittorio Calabrese
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oxidative stress ,inflammation ,neurodegeneration ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Traumatic brain injuries (TBI) are a serious public-health problem. Furthermore, subsequent TBI events can compromise TBI patients’ quality of life. TBI is linked to a number of long- and short-term complications such as cerebral atrophy and risk of developing dementia and Alzheimer’s Disease (AD). Following direct TBI damage, oxidative stress and the inflammatory response lead to tissue injury-associated neurodegenerative processes that are characteristic of TBI-induced secondary damage. Hidrox® showed positive effects in preclinical models of toxic oxidative stress and neuroinflammation; thus, the aim of this study was to evaluate the effect of Hidrox® administration on TBI-induced secondary injury and on the propagation of the AD-like neuropathology. Hidrox® treatment reduced histological damage after controlled cortical impact. Form a molecular point of view, hydroxytyrosol is able to preserve the cellular redox balance and protein homeostasis by activating the Nrf2 pathway and increasing the expression of phase II detoxifying enzymes such as HO-1, SOD, Catalase, and GSH, thus counteracting the neurodegenerative damage. Additionally, Hidrox® showed anti-inflammatory effects by reducing the activation of the NFkB pathway and related cytokines overexpression. From a behavioral point of view, Hidrox® treatment ameliorated the cognitive dysfunction and memory impairment induced by TBI. Additionally, Hidrox® was associated with a significant increased number of hippocampal neurons in the CA3 region, which were reduced post-TBI. In particular, Hidrox® decreased AD-like phenotypic markers such as ß-amyloid accumulation and APP and p-Tau overexpression. These findings indicate that Hidrox® could be a valuable treatment for TBI-induced secondary injury and AD-like pathological features.
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- 2021
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22. PARP-14 Promotes Survival of Mammalian α but Not β Pancreatic Cells Following Cytokine Treatment
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Floriana D'Angeli, Marina Scalia, Matilde Cirnigliaro, Cristina Satriano, Vincenza Barresi, Nicolò Musso, Angela Trovato-Salinaro, Davide Barbagallo, Marco Ragusa, Cinzia Di Pietro, Michele Purrello, and Vittoria Spina-Purrello
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PARP-14 ,JNK1 ,JNK2 ,cytokines ,PJ-34 ,survival ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
PARP-14 (poly-ADP Ribose Polymerase-14), a member of the PARP family, belongs to the group of Bal proteins (B Aggressive Lymphoma). PARP-14 has recently appeared to be involved in the transduction pathway mediated by JNKs (c Jun N terminal Kinases), among which JNK2 promotes cancer cell survival. Several pharmacological PARP inhibitors are currently used as antitumor agents, even though they have also proved to be effective in many inflammatory diseases. Cytokine release from immune system cells characterizes many autoimmune inflammatory disorders, including type I diabetes, in which the inflammatory state causes β cell loss. Nevertheless, growing evidence supports a concomitant implication of glucagon secreting α cells in type I diabetes progression. Here, we provide evidence on the activation of a survival pathway, mediated by PARP-14, in pancreatic α cells, following treatment of αTC1.6 glucagonoma and βTC1 insulinoma cell lines with a cytokine cocktail: interleukin 1 beta (IL-1β), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). Through qPCR, western blot and confocal analysis, we demonstrated higher expression levels of PARP-14 in αTC1.6 cells with respect to βTC1 cells under inflammatory stimuli. By cytofluorimetric and caspase-3 assays, we showed the higher resistance of α cells compared to β cells to apoptosis induced by cytokines. Furthermore, the ability of PJ-34 to modulate the expression of the proteins involved in the survival pathway suggests a protective role of PARP-14. These data shed light on a poorly characterized function of PARP-14 in αTC1.6 cells in inflammatory contexts, widening the potential pharmacological applications of PARP inhibitors.
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- 2019
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23. ATOX1 gene silencing increases susceptibility to anticancer therapy based on copper ionophores or chelating drugs
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Barresi, Vincenza, Spampinato, Giorgia, Musso, Nicolò, Trovato Salinaro, Angela, Rizzarelli, Enrico, and Condorelli, Daniele Filippo
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- 2016
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24. Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis
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Ines Amara, Maria Laura Ontario, Maria Scuto, Gianluigi Maria Lo Dico, Sebastiano Sciuto, Valentina Greco, Salwa Abid-Essefi, Anna Signorile, Angela Trovato Salinaro, and Vittorio Calabrese
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di-(2-ethylhexyl) phthalate ,Moringa oleifera ,endoplasmic reticulum stress ,vitagenes ,oxidative stress ,apoptosis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Moringa oleifera (MO) is a medicinal plant that has been shown to possess antioxidant, anticarcinogenic and antibiotic activities. In a rat model, MO extract (MOe) has been shown to have a protective effect against brain damage and memory decline. As an extending study, here, we have examined the protective effect of MOe against oxidative stress and apoptosis caused in human neuroblastome (SH-SY5Y) cells by di-(2-ethylhexyl) phthalate (DEHP), a plasticizer known to induce neurotoxicity. Our data show that MOe prevents oxidative damage by lowering reactive oxygen species (ROS) formation, restoring mitochondrial respiratory chain complex activities, and, in addition, by modulating the expression of vitagenes, i.e., antioxidant proteins Nrf2 and HO-1. Moreover, MOe prevented neuronal damage by partly inhibiting endoplasmic reticulum (ER) stress response, as indicated by decreased expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and Glucose-regulated protein 78 (GRP78) proteins. MOe also protected SH-SY5Y cells from DEHP-induced apoptosis, preserving mitochondrial membrane permeability and caspase-3 activation. Our findings provide insight into understanding of molecular mechanisms involved in neuroprotective effects by MOe against DEHP damage.
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- 2021
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25. Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology
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Maria Scuto, Maria Laura Ontario, Angela Trovato Salinaro, Isabella Caligiuri, Francesco Rampulla, Vincenzo Zimbone, Sergio Modafferi, Flavio Rizzolio, Vincenzo Canzonieri, Edward J. Calabrese, Vittorio Calabrese, Scuto, Maria, Ontario, Maria Laura, Salinaro, Angela Trovato, Caligiuri, Isabella, Rampulla, Francesco, Zimbone, Vincenzo, Modafferi, Sergio, Rizzolio, Flavio, Canzonieri, Vincenzo, Calabrese, Edward J, and Calabrese, Vittorio
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Polyphenol ,Organoid ,Technology ,Fibromyalgia ,NF-E2-Related Factor 2 ,Hormesi ,Pain ,Settore BIO/11 - Biologia Molecolare ,Mini-brain cancer organoid ,Brain tumors ,Chemoprevention ,Biochemistry ,Antioxidants ,Nanoparticle ,Hormesis ,Vitagenes ,Physiology (medical) ,Humans ,Mini-brain cancer organoids ,WNT/β-catenin pathway ,Vitagene ,Nrf2 pathway ,Nanoparticles ,Oxidative stress ,Polyphenols ,Brain ,Oxidation-Reduction ,Oxidative Stress ,Organoids ,Oxidative Stre ,Brain tumor ,Antioxidant ,Human - Abstract
The scientific community, recently, has focused notable attention on the chemopreventive and therapeutic effects of dietary polyphenols for human health. Emerging evidence demonstrates that polyphenols, flavonoids and vitamins counteract and neutralize genetic and environmental stressors, particularly oxidative stress and inflammatory process closely connected to cancer initiation, promotion and progression. Interestingly, polyphenols can exert antioxidant or pro-oxidant cytotoxic effects depending on their endogenous concentration. Notably, polyphenols at high dose act as pro-oxidants in a wide type of cancer cells by inhibiting Nrf2 pathway and the expression of antioxidant vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), GPx, heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system which play an essential role in the metabolism of reactive oxygen species (ROS), detoxification of xenobiotics and inhibition of cancer progression, by inducing apoptosis and cell cycle arrest according to the hormesis approach. Importantly, mutagenesis of Nrf2 pathway can exacerbate its "dark side" role, representing a crucial event in the initiation stage of carcinogenesis. Herein, we review the hormetic effects of polyphenols and nanoincapsulated-polyphenols in chemoprevention and treatment of brain tumors via activation or inhibition of Nrf2/vitagenes to suppress carcinogenesis in the early stages, and thus inhibit its progression. Lastly, we discuss innovative preclinical approaches through mini-brain tumor organoids to study human carcinogenesis, from basic cancer research to clinical practice, as promising tools to recapitulate the arrangement of structural neuronal tissues and biological functions of the human brain, as well as test drug toxicity and drive personalized and precision medicine in brain cancer.
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- 2022
26. Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis
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Vittorio Calabrese, Maria Scuto, Angela Trovato Salinaro, Giuseppe Dionisio, Sergio Modafferi, Maria Laura Ontario, Valentina Greco, Sebastiano Sciuto, Claus Peter Schmitt, Edward J. Calabrese, and Verena Peters
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carnosine ,hydrogen sulfide ,inflammation ,oxidative stress ,vitagenes ,kidney–brain axis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation of redox-dependent resilience pathways during oxidative stress and inflammation. Several recent studies have elucidated a functional crosstalk occurring between kidney and the brain. The pathophysiological link of this crosstalk is represented by oxidative stress and inflammatory processes which contribute to the high prevalence of neuropsychiatric disorders, cognitive impairment, and dementia during the natural history of chronic kidney disease. Herein, we provide an overview of the main pathophysiological mechanisms related to high levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and neurotoxins, which play a critical role in the kidney–brain crosstalk. The present paper also explores the respective role of H2S and carnosine in the modulation of oxidative stress and inflammation in the kidney–brain axis. It suggests that these activities are likely mediated, at least in part, via hormetic processes, involving Nrf2 (Nuclear factor-like 2), Hsp 70 (heat shock protein 70), SIRT-1 (Sirtuin-1), Trx (Thioredoxin), and the glutathione system. Metabolic interactions at the kidney and brain axis level operate in controlling and reducing oxidant-induced inflammatory damage and therefore, can be a promising potential therapeutic target to reduce the severity of renal and brain injuries in humans.
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- 2020
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27. Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress
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Maria Scuto, Angela Trovato Salinaro, Sergio Modafferi, Alessandra Polimeni, Tilman Pfeffer, Tim Weigand, Vittorio Calabrese, Claus Peter Schmitt, and Verena Peters
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carnosine ,glucose ,diabetic nephropathy cellular stress response ,oxidative stress ,vitagenes ,Biology (General) ,QH301-705.5 - Abstract
Carnosine improves diabetic complications, including diabetic nephropathy, in in vivo models. To further understand the underlying mechanism of nephroprotection, we studied the effect of carnosine under glucose-induced stress on cellular stress response proteins in murine immortalized podocytes, essential for glomerular function. High-glucose stress initiated stress response by increasing intracellular heat shock protein 70 (Hsp70), sirtuin-1 (Sirt-1), thioredoxin (Trx), glutamate-cysteine ligase (gamma-glutamyl cysteine synthetase; γ-GCS) and heme oxygenase-1 (HO-1) in podocytes by 30–50% compared to untreated cells. Carnosine (1 mM) also induced a corresponding upregulation of these intracellular stress markers, which was even more prominent compared to glucose for Hsp70 (21%), γ-GCS and HO-1 (13% and 20%, respectively; all p < 0.001). Co-incubation of carnosine (1 mM) and glucose (25 mM) induced further upregulation of Hsp70 (84%), Sirt-1 (52%), Trx (35%), γ-GCS (90%) and HO-1 (73%) concentrations compared to untreated cells (all p < 0.001). The glucose-induced increase in 4-hydroxy-trans-2-nonenal (HNE) and protein carbonylation was reduced dose-dependently by carnosine by more than 50% (p < 0.001). Although podocytes tolerated high carnosine concentrations (10 mM), high carnosine levels only slightly increased Trx and γ-GCS (10% and 19%, respectively, compared to controls; p < 0.001), but not Hsp70, Sirt-1 and HO-1 proteins (p not significant), and did not modify the glucose-induced oxidative stress response. In podocytes, carnosine induced cellular stress tolerance and resilience pathways and was highly effective in reducing high-glucose-induced glycative and lipoperoxidative stress. Carnosine in moderate concentrations exerted a direct podocyte molecular protective action.
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- 2020
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28. Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson’s Models
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Gabriele Di Rosa, Giovanni Brunetti, Maria Scuto, Angela Trovato Salinaro, Edward J. Calabrese, Roberto Crea, Christian Schmitz-Linneweber, Vittorio Calabrese, and Nadine Saul
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C. elegans ,polyphenols ,olive oil ,healthspan ,lifespan ,ageing ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Parkinson’s disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years. Thus, in the current study we test the health-promoting effects of two hydroxytyrosol preparations, pure HT and Hidrox® (HD), which is hydroxytyrosol in its “natural” environment, in the established invertebrate model organism Caenorhabditis elegans. HD exposure led to much stronger beneficial locomotion effects in wild type worms compared to HT in the same concentration. Consistent to this finding, in OW13 worms, a PD-model characterized by α-synuclein expression in muscles, HD exhibited a significant higher effect on α-synuclein accumulation and swim performance than HT, an effect partly confirmed also in swim assays with the UA44 strain, which features α-synuclein expression in DA-neurons. Interestingly, beneficial effects of HD and HT treatment with similar strength were detected in the lifespan and autofluorescence of wild-type nematodes, in the neuronal health of UA44 worms as well as in the locomotion of rotenone-induced PD-model. Thus, the hypothesis that HD features higher healthspan-promoting abilities than HT was at least partly confirmed. Our study demonstrates that HD polyphenolic extract treatment has the potential to partly prevent or even treat ageing-related neurodegenerative diseases and ageing itself. Future investigations including mammalian models and human clinical trials are needed to uncover the full potential of these olive compounds.
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- 2020
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29. Hericium Erinaceus Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells
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Ines Amara, Maria Scuto, Agata Zappalà, Maria Laura Ontario, Antonio Petralia, Salwa Abid-Essefi, Luigi Maiolino, Anna Signorile, Angela Trovato Salinaro, and Vittorio Calabrese
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di (2-ethylhexyl) pthalate ,hericium erinaceus ,vitagenes ,oxidative stress ,apoptosis ,mitochondrial respiratory complexes ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Hericium Erinaceus (HE) is a medicinal plant known to possess anticarcinogenic, antibiotic, and antioxidant activities. It has been shown to have a protective effect against ischemia-injury-induced neuronal cell death in rats. As an extending study, here we examined in pheochromocytoma 12 (PC12) cells, whether HE could exert a protective effect against oxidative stress and apoptosis induced by di(2-ethylhexyl)phthalate (DEHP), a plasticizer known to cause neurotoxicity. We demonstrated that pretreatment with HE significantly attenuated DEHP induced cell death. This protective effect may be attributed to its ability to reduce intracellular reactive oxygen species levels, preserving the activity of respiratory complexes and stabilizing the mitochondrial membrane potential. Additionally, HE pretreatment significantly modulated Nrf2 and Nrf2-dependent vitagenes expression, preventing the increase of pro-apoptotic and the decrease of anti-apoptotic markers. Collectively, our data provide evidence of new preventive nutritional strategy using HE against DEHP-induced apoptosis in PC12 cells.
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- 2020
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30. Nutritional Mushroom Treatment in Meniere’s Disease with Coriolus versicolor: A Rationale for Therapeutic Intervention in Neuroinflammation and Antineurodegeneration
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Maria Scuto, Paola Di Mauro, Maria Laura Ontario, Chiara Amato, Sergio Modafferi, Domenico Ciavardelli, Angela Trovato Salinaro, Luigi Maiolino, and Vittorio Calabrese
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redoxomics ,glutathione ,meniere’s disease ,neurodegenerative diseases ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Meniere’s disease (MD) represents a clinical syndrome characterized by episodes of spontaneous vertigo, associated with fluctuating, low to medium frequencies sensorineural hearing loss (SNHL), tinnitus, and aural fullness affecting one or both ears. To date, the cause of MD remains substantially unknown, despite increasing evidence suggesting that oxidative stress and neuroinflammation may be central to the development of endolymphatic hydrops and consequent otholitic degeneration and displacement in the reuniting duct, thus originating the otolithic crisis from vestibular otolithic organs utricle or saccule. As a starting point to withstand pathological consequences, cellular pathways conferring protection against oxidative stress, such as vitagenes, are also induced, but at a level not sufficient to prevent full neuroprotection, which can be reinforced by exogenous nutritional approaches. One emerging strategy is supplementation with mushrooms. Mushroom preparations, used in traditional medicine for thousands of years, are endowed with various biological actions, including antioxidant, immunostimulatory, hepatoprotective, anticancer, as well as antiviral effects. For example, therapeutic polysaccharopeptides obtained from Coriolus versicolor are commercially well established. In this study, we examined the hypothesis that neurotoxic insult represents a critical primary mediator operating in MD pathogenesis, reflected by quantitative increases of markers of oxidative stress and cellular stress response in the peripheral blood of MD patients. We evaluated systemic oxidative stress and cellular stress response in MD patients in the absence and in the presence of treatment with a biomass preparation from Coriolus. Systemic oxidative stress was estimated by measuring, in plasma, protein carbonyls, hydroxynonenals (HNE), and ultraweak luminescence, as well as by lipidomics analysis of active biolipids, such as lipoxin A4 and F2-isoprostanes, whereas in lymphocytes we determined heat shock proteins 70 (Hsp72), heme oxygenase-1 (HO-1), thioredoxin (Trx), and γ-GC liase to evaluate the systemic cellular stress response. Increased levels of carbonyls, HNE, luminescence, and F2-isoprostanes were found in MD patients with respect to the MD plus Coriolus-treated group. This was paralleled by a significant (p < 0.01) induction, after Coriolus treatment, of vitagenes such as HO-1, Hsp70, Trx, sirtuin-1, and γ-GC liase in lymphocyte and by a significant (p < 0.05) increase in the plasma ratio-reduced glutathione (GSH) vs. oxidized glutathione (GSSG). In conclusion, patients affected by MD are under conditions of systemic oxidative stress, and the induction of vitagenes after mushroom supplementation indicates a maintained response to counteract intracellular pro-oxidant status. The present study also highlights the importance of investigating MD as a convenient model of cochlear neurodegenerative disease. Thus, searching innovative and more potent inducers of the vitagene system can allow the development of pharmacological strategies capable of enhancing the intrinsic reserve of vulnerable neurons, such as ganglion cells to maximize antidegenerative stress responses and thus providing neuroprotection.
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- 2019
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31. Changes in the Biomarkers of Oxidative/Nitrosative Stress and Endothelial Dysfunction Are Associated with Cardiovascular Risk in Periodontitis Patients
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Maria Paola Bertuccio, Riccardo Ientile, Angela Alibrandi, Monica Currò, Nadia Ferlazzo, Gaetano Isola, Silvia Maggio, Giovanni Matarese, Angela Trovato-Salinaro, and Daniela Caccamo
- Subjects
3-nitrotyrosine (NT) ,Asymmetric dimethylarginine (ADMA) ,Cardiovascular disease ,Coen-zyme Q10 (CoQ10) ,Inflammasome ,Periodontitis (PT) ,Peripheral blood mononuclear cells (PBMC) ,Cardiovascular Diseases ,Case-Control Studies ,Disease Susceptibility ,Endothelium ,Heart Disease Risk Factors ,Humans ,Leukocytes, Mononuclear ,Periodontitis ,ROC Curve ,Risk Assessment ,Risk Factors ,Biomarkers ,Nitrosative Stress ,Oxidative Stress ,0301 basic medicine ,030204 cardiovascular system & hematology ,medicine.disease_cause ,periodontitis (PT) ,Pathogenesis ,chemistry.chemical_compound ,0302 clinical medicine ,cardiovascular disease ,Medicine ,Biology (General) ,Endothelial dysfunction ,General Medicine ,coenzyme Q10 (CoQ10) ,Tumor necrosis factor alpha ,Microbiology (medical) ,medicine.medical_specialty ,QH301-705.5 ,asymmetric dimethylarginine (ADMA) ,Microbiology ,Peripheral blood mononuclear cell ,03 medical and health sciences ,inflammasome ,Internal medicine ,Molecular Biology ,Coenzyme Q10 ,business.industry ,medicine.disease ,030104 developmental biology ,Endocrinology ,chemistry ,peripheral blood mononuclear cells (PBMC) ,business ,Asymmetric dimethylarginine ,Oxidative stress - Abstract
Patients with cardiovascular disease (CVD) and periodontitis (PT) show shared risk factors as result of the altered molecular mechanisms associated with pathological conditions. The aim of our study was to evaluate if the plasma biomarkers associated with endothelial dysfunction may also be related to alterations in the inflammatory status in peripheral blood mononuclear cells (PBMC). Patients with PT, coronary heart disease (CHD), or both diseases as well as controls were enrolled. Plasma levels of coenzyme Q10 (CoQ10), 3-nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) were assessed using HPLC. mRNA levels of caspase-1 (CASP1), NLR family pyrin domain containing 3 (NLRP3), and tumor necrosis factor-α (TNF-α) in PBMC from the recruited subjects were quantified using real-time PCR. Patients with PT + CHD showed lower CoQ10 plasma levels and increased concentrations of NT in comparison to healthy subjects. ADMA levels were higher in CHD and PT + CHD patients compared to controls. Transcript levels of CASP1, NLRP3, and TNF-α were up-regulated in PBMC from all patient groups when compared to healthy subjects. Our results suggest a possible causal link between oxidative stress, high levels of NT and ADMA, and inflammasome activation, which may be involved in the endothelial inflammatory dysfunction leading to the pathogenesis and progression of CHD in PT patients.
- Published
- 2021
32. Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: modulation by nutritional mushrooms
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Trovato Salinaro, Angela, Pennisi, Manuela, Di Paola, Rosanna, Scuto, Maria, Crupi, Rosalia, Cambria, Maria Teresa, Ontario, Maria Laura, Tomasello, Mario, Uva, Maurizio, Maiolino, Luigi, Calabrese, Edward J., Cuzzocrea, Salvatore, and Calabrese, Vittorio
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- 2018
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33. Rotenone-induced oxidative stress in THP-1 cells: biphasic effects of baicalin
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Monica Currò, Caterina Saija, Alessandra Trainito, Angela Trovato-Salinaro, Maria Paola Bertuccio, Giuseppa Visalli, Daniela Caccamo, and Riccardo Ientile
- Subjects
Genetics ,General Medicine ,Molecular Biology - Abstract
Several results demonstrated that microglia and peripheral monocytes/macrophages infiltrating the central nervous system (CNS) are involved in cell response against toxic compounds. It has been shown that rotenone induces neurodegeneration in various in vitro experimental models. Baicalin, a natural compound, is able to attenuate cell damage through anti-oxidant, anti-microbial, anti-inflammatory, and immunomodulatory action. Using THP-1 monocytes, we investigated rotenone effects on mitochondrial dysfunction and apoptosis, as well as baicalin ability to counteract rotenone toxicity.THP-1 cells were exposed to rotenone (250 nM), in the presence/absence of baicalin (10-500 μM) for 2-24 h. Reactive Oxygen Species production (ROS), mitochondrial activity and transmembrane potential (Δψm), DNA damage, and caspase-3 activity were assessed. Moreover, gene expression of mitochondrial transcription factor a (mtTFA), interleukin-1β (IL-1β), B-cell lymphoma 2 (Bcl2) and BCL2-associated X protein (Bax), together with apoptotic morphological changes, were evaluated. After 2 h of rotenone incubation, increased ROS production and altered Δψm were observed, hours later resulting in DNA oxidative damage and apoptosis. Baicalin treatment at 50 µM counteracted rotenone toxicity by modulating the expression levels of some proteins involved in mitochondrial biogenesis and apoptosis. Interestingly, at higher baicalin concentrations, rotenone-induced alterations persisted.These results give evidence that exposure to rotenone may promote the activation of THP-1 monocytes contributing to enhanced neurodegeneration. In this context, baicalin at low concentration exerts beneficial effects on mitochondrial function, and thus may prevent the onset of neurotoxic processes.
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- 2022
34. Curcumin, Hormesis and the Nervous System
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Maria Concetta Scuto, Cesare Mancuso, Barbara Tomasello, Maria Laura Ontario, Andrea Cavallaro, Francesco Frasca, Luigi Maiolino, Angela Trovato Salinaro, Edward J. Calabrese, and Vittorio Calabrese
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hormesis ,vitagenes ,antioxidants ,heme oxygenase ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Curcumin is a polyphenol compound extracted from the rhizome of Curcuma longa Linn (family Zingiberaceae) commonly used as a spice to color and flavor food. Several preclinical studies have suggested beneficial roles for curcumin as an adjuvant therapy in free radical-based diseases, mainly neurodegenerative disorders. Indeed, curcumin belongs to the family of hormetins and the enhancement of the cell stress response, mainly the heme oxygenase-1 system, is actually considered the common denominator for this dual response. However, evidence-based medicine has clearly demonstrated the lack of any therapeutic effect of curcumin to contrast the onset or progression of neurodegeneration and related diseases. Finally, the curcumin safety profile imposes a careful analysis of the risk/benefit balance prior to proposing chronic supplementation with curcumin.
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- 2019
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35. Redox modulation of stress resilience by Crocus sativus L. for potential neuroprotective and anti-neuroinflammatory applications in brain disorders: From molecular basis to therapy
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M. Scuto, S. Modafferi, F. Rampulla, V. Zimbone, M. Tomasello, S. Spano’, M.L. Ontario, A. Palmeri, A. Trovato Salinaro, R. Siracusa, R. Di Paola, S. Cuzzocrea, E.J. Calabrese, U. Wenzel, and V. Calabrese
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Aging ,Brain Diseases ,NF-E2-Related Factor 2 ,Plant Extracts ,Humans ,Crocus ,Oxidation-Reduction ,Antioxidants ,Developmental Biology - Abstract
Recent evidence demonstrates that Crocus sativus L. (saffron) counteracts oxidative stress, mitochondrial dysfunction and neuroinflammation, closely linked to initiation and progression of major brain pathologies. Interestingly, saffron constituents such as crocin, crocetin and safranal can exert antioxidant or toxic effects depending on their endogenous concentration. According to the hormesis principles, at low dose they act as antioxidants in a wide range of brain diseases by upregulating Nrf2 signaling pathway and the expression of vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system. Importantly, neuronal dysregulation of Nrf2 pathway can be a prominent cause of selective susceptibility, under neuroinflammatory conditions, due to the high vulnerability of brain cells to oxidative stress. Here we discuss natural inducers from saffron targeting Nrf2/vitagene pathway for development of new therapeutical strategies to suppress oxidative stress and neuroinflammation and consequently cognitive dysfunction. In this review we also focus on the hormetic effect of saffron active constituents, summarizing their neuroprotective and anti-neuroinflammatory properties, as well as pharmacological perspectives in brain disorders.
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- 2022
36. Design, synthesis and in vitro antitumour activity of new heteroaryl ethylenes
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Fortuna, Cosimo G., Barresi, Vincenza, Bonaccorso, Carmela, Consiglio, Giuseppe, Failla, Salvatore, Trovato-Salinaro, Angela, and Musumarra, Giuseppe
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- 2012
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37. Redox modulation of vitagenes via plant polyphenols and vitamin D: Novel insights for chemoprevention and therapeutic interventions based on Organoid Technology
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Maria Scuto, Isabella Caligiuri, Vincenzo Canzonieri, Maria Laura Ontario, Angela Trovato Salinaro, Vittorio Calabrese, Nello Sciuto, Edward J. Calabrese, Roberto Crea, Valentina Greco, Flavio Rizzolio, Scuto, M., Trovato Salinaro, A., Caligiuri, I., Ontario, M. L., Greco, V., Sciuto, N., Crea, R., Calabrese, E. J., Rizzolio, F., Canzonieri, V., and Calabrese, V.
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Organoid ,Aging ,Plant polyphenol ,Anti-Inflammatory Agents ,vitamin D ,Personalized therapy ,Resveratrol ,medicine.disease_cause ,Antioxidants ,chemistry.chemical_compound ,Autophagy process ,Cancer ,Chemoprevention ,Organoids ,Plant polyphenols ,Vitagenes ,Vitamin D ,Phytogenic ,Neoplasms ,chemoprevention ,organoids ,Vitagene ,Animals ,Antineoplastic Agents, Phytogenic ,COVID-19 ,Humans ,NF-E2-Related Factor 2 ,Oxidation-Reduction ,Oxidative Stress ,Polyphenols ,Drug Development ,autophagy process ,vitagenes ,plant polyphenols ,Antineoplastic Agents ,Settore BIO/11 - Biologia Molecolare ,Autophagy proce ,Heat shock protein ,medicine ,cancer ,personalized therapy ,Autophagy ,medicine.disease ,COVID-19 Drug Treatment ,chemistry ,Cancer cell ,Cancer research ,Curcumin ,Carcinogenesis ,Oxidative stress ,Developmental Biology - Abstract
Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)-mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Here, the importance of vitagenes in redox stress response and autophagy mechanisms, as well as the potential use of dietary antioxidants in the prevention and treatment of multiple types of cancer are discussed. We also discuss the possible relationship between SARS-CoV-2, inflammation and cancer, exploiting innovative therapeutic approaches with HT-rich aqueous olive pulp extract (Hidrox®), a natural polyphenolic formulation, as well as the rationale of Vitamin D supplementation. Finally, we describe innovative approaches with organoids technology to study human carcinogenesis in preclinical models from basic cancer research to clinical practice, suggesting patient-derived organoids as an innovative tool to test drug toxicity and drive personalized therapy.
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- 2021
38. Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease
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Roberta Fusco, Vittorio Calabrese, Maria Scuto, Maria Laura Ontario, Rosanna Di Paola, Angela Trovato Salinaro, Rosalba Siracusa, Daniela Impellizzeri, Salvatore Cuzzocrea, Ramona D'Amico, and Marika Cordaro
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Antioxidant ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Hippocampus ,Inflammation ,RM1-950 ,Pharmacology ,Biology ,Hippocampal formation ,medicine.disease_cause ,Biochemistry ,Article ,Alzheimer’s disease ,Inflammasome ,Oxidative stress ,inflammasome ,medicine ,oxidative stress ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Biology ,biology.organism_classification ,chemistry ,Therapeutics. Pharmacology ,medicine.symptom ,Hericium erinaceus ,medicine.drug - Abstract
Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and Hericium erinaceus was administered daily by gavage. Before the experiment’s end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. Hericium erinaceus administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, Hericium erinaceus decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that Hericium erinaceus has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress.
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- 2021
39. Potential prevention and treatment of neurodegenerative disorders by olive polyphenols and hidrox
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Maria Laura Ontario, Rosalba Siracusa, Sergio Modafferi, Maria Scuto, Sebastiano Sciuto, Valentina Greco, Maria Paola Bertuccio, Angela Trovato Salinaro, Roberto Crea, Edward J. Calabrese, Rosanna Di Paola, and Vittorio Calabrese
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Aging ,Biological Products ,Kelch-Like ECH-Associated Protein 1 ,NF-E2-Related Factor 2 ,Polyphenols ,Neurodegenerative Diseases ,Hidrox ,Personalized therapy ,Oxidative Stress ,Plant polyphenols ,Vitagenes ,Olea ,Neurodegenerative disorders ,Humans ,Developmental Biology - Abstract
Most chronic illnesses are caused by the biological reaction to an injury, rather than the initial injury or the injurious agent itselves as in neurodegeneration. With respect to this, notable attention is emerging on the therapeutic effects of dietary polyphenols for human health, able to counteract and neutralize oxidative stress and inflammatory processes involved in the etiopathogenesis of major neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. The acquired concept that cellular stress at low doses induces neuroprotective responses against degenerative processes is a frontier area of the neurobiological research focusing on the development of novel preventive and therapeutic interventions for neurodegenerative disorders. Notably, basal levels of prooxidant species are essential to promote adaptive redox cellular responses including vitagenes, tightly correlated to cell survival against age-related diseases. In this paper we discuss the concept of cellular stress response and hormesis and its applications to the field of neuroprotection and the potential therapeutic support provided by olive polyphenols, in particular hydroxytyrosol (HT)-rich aqueous olive pulp extract (Hidrox), as a pivotal activator of Nrf2 pathway and related vitagenes, and inhibitor of Keap1-Nrf2 interaction.Olive polyphenols are considered potential pharmacological modulators of neuroinflammation by upregulation of the Keap1/Nfr2/ARE pathway thus providing a strong rationale for treating neurodegenerative disorders.
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- 2021
40. Pericytes of Stria Vascularis Are Targets of Cisplatin-Induced Ototoxicity: New Insights into the Molecular Mechanisms Involved in Blood-Labyrinth Barrier Breakdown.
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Anfuso, Carmelina Daniela, Cosentino, Alessia, Agafonova, Aleksandra, Zappalà, Agata, Giurdanella, Giovanni, Trovato Salinaro, Angela, Calabrese, Vittorio, and Lupo, Gabriella
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PERICYTES ,VASCULAR endothelial growth factors ,PLATELET-derived growth factor ,CYCLOOXYGENASE 2 ,OTOTOXICITY ,COCHLEA physiology ,HOMEOSTASIS - Abstract
The stria vascularis (SV) contributes to cochlear homeostasis and consists of three layers, one of which contains the blood-labyrinthic barrier (BLB), with a large number of bovine cochlear pericytes (BCPs). Cisplatin is a chemotherapeutic drug that can damage the SV and cause hearing loss. In this study, cell viability, proliferation rate, cytotoxicity and reactive oxygen species production were evaluated. The protein content of phospho-extracellular signal-regulated kinases (ERK) 1/2, total ERK 1/2, phospho-cytosolic phospholipase A
2 (cPLA2 ), total cPLA2 and cyclooxygenase 2 (COX-2) and the release of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) from BCPs were analyzed. Finally, the protective effect of platelet-derived growth factor (PDGF-BB) on BCPs treated with cisplatin was investigated. Cisplatin reduced viability and proliferation, activated ERK 1/2, cPLA2 and COX-2 expression and increased PGE2 and VEGF release; these effects were reversed by Dexamethasone. The presence of PDGF-BB during the treatment with cisplatin significantly increased the proliferation rate. No studies on cell regeneration in ear tissue evaluated the effect of the PDGF/Dex combination. The aim of this study was to investigate the effects of cisplatin on cochlear pericytes and propose new otoprotective agents aimed at preventing the reduction of their vitality and thus maintaining the BLB structure. [ABSTRACT FROM AUTHOR]- Published
- 2022
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41. Autophagy and Mitophagy Promotion in a Rat Model of Endometriosis
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Rosalia Crupi, Rosanna Di Paola, Emanuela Raffone, Alessio Filippo Peritore, Salvatore Cuzzocrea, Roberta Fusco, Rosalba Siracusa, Marika Cordaro, Daniela Impellizzeri, Ramona D'Amico, Tiziana Genovese, Angela Trovato Salinaro, and Enrico Gugliandolo
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Autophagy ,Endometriosis ,Mitophagy ,endometriosis ,autophagy ,QH301-705.5 ,Angiogenesis ,Apoptosis ,Catalysis ,Parkin ,Article ,Inorganic Chemistry ,Rats, Sprague-Dawley ,Western blot ,Medicine ,Animals ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,PI3K/AKT/mTOR pathway ,medicine.diagnostic_test ,business.industry ,Kinase ,TOR Serine-Threonine Kinases ,Organic Chemistry ,General Medicine ,Computer Science Applications ,Rats ,Chemistry ,mitophagy ,Cancer research ,Female ,business - Abstract
Endometriosis is a gynecological condition affecting patients in reproductive age. The aim of this paper was to assess the effects of the autophagy and mitophagy induction in a rat model of endometriosis. Endometriosis was induced by the injection of uterine fragments, and rapamycin (0. 5 mg/kg) was administered once per week. One week from the induction, rats were sacrificed, and laparotomy was performed to collect the endometriotic implants and to further process them for molecular analysis. Western blot analysis was conducted on explanted lesions to evaluate the autophagy pathway during the pathology. Elevated phospho-serine/threonine kinase (p-AKT) and mammalian target of rapamycin (mTOR) expressions were detected in vehicle-treated rats, while Beclin and microtubule-associated protein 1A/1B-light chain 3 II (LC3II) expressions were low. Additionally, samples collected from vehicle groups indicated low Bnip3, Ambra1, and Parkin expressions, demonstrating impaired autophagy and mitophagy. Rapamycin administration reduced p-AKT and mTOR expressions and increased Beclin and LC3II, Bnip3, Ambra1, and Parkin expressions, activating both mechanisms. We also evaluated the impact of the impaired autophagy and mitophagy pathways on apoptosis and angiogenesis. Rapamycin was administered by activating autophagy and mitophagy, which increased apoptosis (assessed by Western blot analysis of Bcl-2, Bax, and Cleaved-caspase 3) and reduced angiogenesis (assessed by immunohistochemical analysis of vascular endothelial grow factor (VEGF) and CD34) in the lesions. All of these mechanisms activated by the induction of the autophagy and mitophagy pathways led to the reduction in the lesions’ volume, area and diameter.
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- 2021
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42. Hidrox® Roles in Neuroprotection: Biochemical Links between Traumatic Brain Injury and Alzheimer’s Disease
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Rosanna Di Paola, Ramona D'Amico, Maria Scuto, Maria Laura Ontario, Roberto Crea, Daniela Impellizzeri, Marika Cordaro, Vittorio Calabrese, Angela Trovato Salinaro, Roberta Fusco, Rosalba Siracusa, and Salvatore Cuzzocrea
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0301 basic medicine ,Physiology ,Traumatic brain injury ,Clinical Biochemistry ,Neuropathology ,RM1-950 ,Bioinformatics ,medicine.disease_cause ,Biochemistry ,Neuroprotection ,Article ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Dementia ,oxidative stress ,Inflammation ,Neurodegeneration ,Oxidative stress ,Molecular Biology ,Neuroinflammation ,Cerebral atrophy ,business.industry ,neurodegeneration ,Cell Biology ,medicine.disease ,nervous system diseases ,030104 developmental biology ,nervous system ,inflammation ,Therapeutics. Pharmacology ,business ,030217 neurology & neurosurgery - Abstract
Traumatic brain injuries (TBI) are a serious public-health problem. Furthermore, subsequent TBI events can compromise TBI patients’ quality of life. TBI is linked to a number of long- and short-term complications such as cerebral atrophy and risk of developing dementia and Alzheimer’s Disease (AD). Following direct TBI damage, oxidative stress and the inflammatory response lead to tissue injury-associated neurodegenerative processes that are characteristic of TBI-induced secondary damage. Hidrox® showed positive effects in preclinical models of toxic oxidative stress and neuroinflammation, thus, the aim of this study was to evaluate the effect of Hidrox® administration on TBI-induced secondary injury and on the propagation of the AD-like neuropathology. Hidrox® treatment reduced histological damage after controlled cortical impact. Form a molecular point of view, hydroxytyrosol is able to preserve the cellular redox balance and protein homeostasis by activating the Nrf2 pathway and increasing the expression of phase II detoxifying enzymes such as HO-1, SOD, Catalase, and GSH, thus counteracting the neurodegenerative damage. Additionally, Hidrox® showed anti-inflammatory effects by reducing the activation of the NFkB pathway and related cytokines overexpression. From a behavioral point of view, Hidrox® treatment ameliorated the cognitive dysfunction and memory impairment induced by TBI. Additionally, Hidrox® was associated with a significant increased number of hippocampal neurons in the CA3 region, which were reduced post-TBI. In particular, Hidrox® decreased AD-like phenotypic markers such as ß-amyloid accumulation and APP and p-Tau overexpression. These findings indicate that Hidrox® could be a valuable treatment for TBI-induced secondary injury and AD-like pathological features.
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- 2021
43. Moringa oleifera protects sh-sy5ycells from dehp-induced endoplasmic reticulum stress and apoptosis
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Anna Signorile, Valentina Greco, Vittorio Calabrese, Maria Scuto, Maria Laura Ontario, Ines Amara, Angela Trovato Salinaro, Gianluigi Maria Lo Dico, Salwa Abid-Essefi, and Sebastiano Sciuto
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0301 basic medicine ,Antioxidant ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Apoptosis ,medicine.disease_cause ,Biochemistry ,Neuroprotection ,Article ,Mitochondrial respiratory complexes ,03 medical and health sciences ,0302 clinical medicine ,Vitagenes ,medicine ,Inner mitochondrial membrane ,Molecular Biology ,chemistry.chemical_classification ,Moringa oleifera ,Reactive oxygen species ,Chemistry ,Endoplasmic reticulum ,lcsh:RM1-950 ,Neurotoxicity ,Cell Biology ,Di-(2-ethylhexyl) phthalate ,medicine.disease ,Cell biology ,030104 developmental biology ,Mitochondrial respiratory chain ,lcsh:Therapeutics. Pharmacology ,Oxidative stress ,Endoplasmic reticulum stress ,030217 neurology & neurosurgery - Abstract
Moringa oleifera (MO) is a medicinal plant that has been shown to possess antioxidant, anticarcinogenic and antibiotic activities. In a rat model, MO extract (MOe) has been shown to have a protective effect against brain damage and memory decline. As an extending study, here, we have examined the protective effect of MOe against oxidative stress and apoptosis caused in human neuroblastome (SH-SY5Y) cells by di-(2-ethylhexyl) phthalate (DEHP), a plasticizer known to induce neurotoxicity. Our data show that MOe prevents oxidative damage by lowering reactive oxygen species (ROS) formation, restoring mitochondrial respiratory chain complex activities, and, in addition, by modulating the expression of vitagenes, i.e., antioxidant proteins Nrf2 and HO-1. Moreover, MOe prevented neuronal damage by partly inhibiting endoplasmic reticulum (ER) stress response, as indicated by decreased expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and Glucose-regulated protein 78 (GRP78) proteins. MOe also protected SH-SY5Y cells from DEHP-induced apoptosis, preserving mitochondrial membrane permeability and caspase-3 activation. Our findings provide insight into understanding of molecular mechanisms involved in neuroprotective effects by MOe against DEHP damage.
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- 2021
44. Atrazine inhalation causes neuroinflammation, apoptosis and accelerating brain aging
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Alessio Filippo Peritore, Rosanna Di Paola, Rosalba Siracusa, Ramona D'Amico, Salvatore Cuzzocrea, Tiziana Genovese, Marika Cordaro, Daniela Impellizzeri, Enrico Gugliandolo, Rossana Morabito, Roberta Fusco, Rosalia Crupi, and Angela Trovato Salinaro
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0301 basic medicine ,Male ,Aging ,QH301-705.5 ,Inflammation ,Apoptosis ,Pharmacology ,medicine.disease_cause ,Catalysis ,Article ,Inorganic Chemistry ,Lipid peroxidation ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Administration, Inhalation ,medicine ,Animals ,Atrazine ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Neuroinflammation ,Inhalation ,business.industry ,Brain alterations ,Endocrine disruptor ,Oxidative stress ,Brain ,Organic Chemistry ,General Medicine ,Computer Science Applications ,Chemistry ,030104 developmental biology ,chemistry ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain’s neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. Methods: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. Results: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. Conclusions: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.
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- 2021
45. Regulation of inflammatory and proliferative pathways by fotemustine and dexamethasone in endometriosis
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Enrico Gugliandolo, Rosalba Siracusa, Rosalia Crupi, Tiziana Genovese, Rosanna Di Paola, Salvatore Cuzzocrea, Emanuela Raffone, Ramona D'Amico, Roberta Fusco, Daniela Impellizzeri, Angela Trovato Salinaro, Alessio Filippo Peritore, and Marika Cordaro
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QH301-705.5 ,Endometriosis ,Inflammation ,Apoptosis ,Pharmacology ,Catalysis ,Article ,Dexamethasone ,Nitrosourea Compounds ,Proinflammatory cytokine ,Inorganic Chemistry ,Pathogenesis ,Endometrium ,Organophosphorus Compounds ,Western blot ,Proliferating Cell Nuclear Antigen ,Medicine ,Animals ,Ascitic Fluid ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Pathways ,Molecular Biology ,QD1-999 ,Spectroscopy ,Cell Proliferation ,medicine.diagnostic_test ,business.industry ,Organic Chemistry ,NF-kappa B ,Transcription Factor RelA ,General Medicine ,Computer Science Applications ,Female ,Rats ,Signal Transduction ,Chemistry ,Fotemustine ,Immunohistochemistry ,medicine.symptom ,business ,medicine.drug - Abstract
Endometriosis is a common disease. Its pathogenesis still remains uncertain, but it is clear that cell proliferation, apoptosis and chronic inflammation play an important role in its development. This paper aimed to investigate the anti-proliferative and anti-inflammatory effects of a combined therapy with fotemustine and dexamethasone. Endometriosis was induced by intraperitoneal injections of uterine fragments from donor animals to recipient animals. Next, the pathology was allowed to develop for 7 days. On the seventh day, fotemustine was administered once and dexamethasone was administered daily for the next 7 days. On Day 14, the animals were sacrificed, and peritoneal fluids and lesions were explanted. In order to evaluate the gastrointestinal side effects of the drugs, stomachs were harvested as well. The combined therapy of fotemustine and dexamethasone reduced the proinflammatory mediator levels in the peritoneal fluid and reduced the lesions’ area and diameter. In particular, fotemustine and dexamethasone administration reduced the heterogeneous development of endometrial stroma and glands (histological analysis of lesions) and hyperproliferation of endometriotic cells (immunohistochemical analysis of Ki67 and Western blot analysis of PCNA) through the mitogen-activated protein kinase (MAPK) signaling pathway. Combined fotemustine and dexamethasone therapy showed anti-inflammatory effects by inducing the synthesis of anti-inflammatory mediators at the transcriptional and post-transcriptional levels (Western blot analysis of NFκB, COX-2 and PGE2 expression). Fotemustine and dexamethasone administration had anti-apoptotic activity, restoring the impaired mechanism (TUNEL assay and Western blot analysis of Bax and Bcl-2). Moreover, no gastric disfunction was detected (histological analysis of stomachs). Thus, our data showed that the combined therapy of fotemustine and dexamethasone reduced endometriosis-induced inflammation, hyperproliferation and apoptosis resistance.
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- 2021
46. Hericium erinaceus and coriolus versicolor modulate molecular and biochemical changes after traumatic brain injury
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Gianluigi Maria Lo Dico, Rosanna Di Paola, Angela Trovato Salinaro, Marika Cordaro, Ramona D'Amico, Rosalba Siracusa, Roberta Fusco, Maria Scuto, Vittorio Calabrese, Maria Laura Ontario, Salvatore Cuzzocrea, and Daniela Impellizzeri
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0301 basic medicine ,Mushrooms ,Physiology ,Traumatic brain injury ,Brain trauma ,Neurodegeneration ,Neuroinflammation ,Oxidative stress ,Clinical Biochemistry ,Substantia nigra ,Context (language use) ,RM1-950 ,Pharmacology ,medicine.disease_cause ,Biochemistry ,Neuroprotection ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Molecular Biology ,biology ,business.industry ,Cell Biology ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,Therapeutics. Pharmacology ,business ,030217 neurology & neurosurgery ,Hericium erinaceus - Abstract
Traumatic brain injury (TBI) is a major health and socioeconomic problem affecting the world. This condition results from the application of external physical force to the brain which leads to transient or permanent structural and functional impairments. TBI has been shown to be a risk factor for neurodegeneration which can lead to Parkinson’s disease (PD) for example. In this study, we wanted to explore the development of PD-related pathology in the context of an experimental model of TBI and the potential ability of Coriolus versicolor and Hericium erinaceus to prevent neurodegenerative processes. Traumatic brain injury was induced in mice by controlled cortical impact. Behavioral tests were performed at various times: the animals were sacrificed 30 days after the impact and the brain was processed for Western blot and immunohistochemical analyzes. After the head injury, a significant decrease in the expression of tyrosine hydroxylase and the dopamine transporter in the substantia nigra was observed, as well as significant behavioral alterations that were instead restored following daily oral treatment with Hericium erinaceus and Coriolus versicolor. Furthermore, a strong increase in neuroinflammation and oxidative stress emerged in the vehicle groups. Treatment with Hericium erinaceus and Coriolus versicolor was able to prevent both the neuroinflammatory and oxidative processes typical of PD. This study suggests that PD-related molecular events may be triggered on TBI and that nutritional fungi such as Hericium erinaceus and Coriolus versicolor may be important in redox stress response mechanisms and neuroprotection, preventing the progression of neurodegenerative diseases such as PD.
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- 2021
47. Xenohormesis underlyes the anti-aging and healthy properties of olive polyphenols
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Monica Bucciantini, Manuela Leri, Maria Scuto, Marialaura Ontario, Angela Trovato Salinaro, Edward J. Calabrese, Vittorio Calabrese, and Massimo Stefani
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olive oil polyphenols ,Aging ,xenohormesis ,Hormesis ,Vitagenes ,Olea ,neurodegeneration ,Humans ,Polyphenols ,Neurodegenerative Diseases ,lifespan ,Developmental Biology - Abstract
The paper provides a comprehensive and foundational mechanistic framework of hormesis that establishes its centrality in medicine and public health. This hormetic framework is applied to the assessment of olive polyphenols with respect to their capacity to slow the onset and reduce the magnitude of a wide range of age-related disorders and neurodegenerative diseases, including Alzheimer's Disease and Parkinson's Disease. It is proposed that olive polyphenol-induced anti-inflammatory protective effects are mediated in large part via the activation of AMPK and the upregulation of Nrf2 pathway. Consistently, herein we also review the importance of the modulation of Nrf2-related stress responsive vitagenes by olive polyphenols, which at low concentration according to the hormesis theory activates this neuroprotective cascade to preserve brain health and its potential use in the prevention and therapy against aging and age-related cognitive disorders in humans.
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- 2022
48. Regulation of connexin gene expression during skeletal muscle regeneration in the adult rat
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Trovato-Salinaro, A., Belluardo, N., Frinchi, M., von Maltzahn, J., Willecke, K., Condorelli, D.F., and Mudo, G.
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Gene expression -- Research ,Muscles -- Genetic aspects ,Muscles -- Regeneration ,Biological sciences - Abstract
In the adult skeletal muscle, various kinds of trauma promote proliferation of satellite cells that differentiate into myoblasts forming new myofibers or to repair the damaged one. The aim of present work was to perform a comparative spatial and temporal analysis of connexin (Cx) 37, Cx39, Cx40, Cx43, and Cx45 expression in the adult regenerating skeletal muscle in response to crush injury. Within 24 h from injury, Cx37 expression was upregulated in the endothelial cells of blood vessels, and, 5 days after injury, Cx37-expressing cells were found inside the area of lesion and formed clusters generating new blood vessels with endothelial cells expressing Cx37. Three days after injury, Cx39 mRNA was selectively expressed in myogenin-positive cells, forming rows of closely apposed cell nuclei fusing in myotubes. Cx40 mRNA-labeled cells were observed within 24 h from injury in the endothelium of blood vessels, and, 5 days after lesion, Cx40-labeled cells were found inside the area of lesion-forming rows of myogenin-positive, closely apposed cells coexpressing Cx39. Within 24 h from lesion, both Cx43 and Cx45 mRNAs were upregulated in individual cells, and some of them were positive for M-cadherin. Three days after injury, a large number of both Cx43 and Cx45 mRNA-labeled and myogenin-positive cells were found inside the area of lesion. Taken together, these results show that at least four Cxs, out of five expressed in regenerating skeletal muscle, can be differentially involved in communication of myogenic cells during the process of cell proliferation, aggregation, and fusion to form new myotubes or to repair damaged myofibers. connexin 37; connexin 39; connexin 40; connexin 43; connexin 45; myogenic cells; muscle regeneration
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- 2009
49. Hericium Erinaceus Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells
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Agata Zappalà, A. Petralia, Salwa Abid-Essefi, Maria Scuto, Maria Laura Ontario, Anna Signorile, Luigi Maiolino, Vittorio Calabrese, Ines Amara, and Angela Trovato Salinaro
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Programmed cell death ,endocrine system ,Antioxidant ,medicine.medical_treatment ,Pharmacology ,medicine.disease_cause ,Article ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,Hericium erinaceus ,medicine ,oxidative stress ,Di (2-Ethylhexyl) pthalate ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Membrane potential ,Hericium ernaceus ,biology ,Organic Chemistry ,Phthalate ,Neurotoxicity ,apoptosis ,General Medicine ,biology.organism_classification ,medicine.disease ,Computer Science Applications ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,Apoptosis ,mitochondrial respiratory complexes ,vitagenes ,Oxidative stress - Abstract
Hericium Erinaceus (HE) is a medicinal plant known to possess anticarcinogenic, antibiotic, and antioxidant activities. It has been shown to have a protective effect against ischemia-injury-induced neuronal cell death in rats. As an extending study, here we examined in pheochromocytoma 12 (PC12) cells, whether HE could exert a protective effect against oxidative stress and apoptosis induced by di(2-ethylhexyl)phthalate (DEHP), a plasticizer known to cause neurotoxicity. We demonstrated that pretreatment with HE significantly attenuated DEHP induced cell death. This protective effect may be attributed to its ability to reduce intracellular reactive oxygen species levels, preserving the activity of respiratory complexes and stabilizing the mitochondrial membrane potential. Additionally, HE pretreatment significantly modulated Nrf2 and Nrf2-dependent vitagenes expression, preventing the increase of pro-apoptotic and the decrease of anti-apoptotic markers. Collectively, our data provide evidence of new preventive nutritional strategy using HE against DEHP-induced apoptosis in PC12 cells.
- Published
- 2020
- Full Text
- View/download PDF
50. Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson’s Models
- Author
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Maria Scuto, Nadine Saul, Giovanni Brunetti, Christian Schmitz-Linneweber, Edward J. Calabrese, Vittorio Calabrese, Gabriele Di Rosa, Angela Trovato Salinaro, and Roberto Crea
- Subjects
Aging ,Parkinson's disease ,Mediterranean diet ,ved/biology.organism_classification_rank.species ,healthspan ,Pharmacology ,Diet, Mediterranean ,lcsh:Chemistry ,Animals, Genetically Modified ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:QH301-705.5 ,Spectroscopy ,Caenorhabditis elegans ,0303 health sciences ,education.field_of_study ,biology ,Parkinson Disease ,General Medicine ,olive oil ,3. Good health ,Computer Science Applications ,C. elegans ,alpha-Synuclein ,polyphenols ,lifespan ,ageing ,Parkinson’s disease ,Population ,Longevity ,570 Biologie ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,ddc:570 ,Olea ,Rotenone ,medicine ,Animals ,Humans ,ddc:610 ,Physical and Theoretical Chemistry ,Model organism ,education ,Caenorhabditis elegans Proteins ,Molecular Biology ,030304 developmental biology ,ved/biology ,Dopaminergic Neurons ,Organic Chemistry ,Wild type ,biology.organism_classification ,medicine.disease ,nervous system diseases ,Disease Models, Animal ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,Microscopy, Fluorescence ,13. Climate action ,Ageing ,Hydroxytyrosol ,610 Medizin und Gesundheit ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Parkinson&rsquo, s disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years. Thus, in the current study we test the health-promoting effects of two hydroxytyrosol preparations, pure HT and Hidrox®, (HD), which is hydroxytyrosol in its &ldquo, natural&rdquo, environment, in the established invertebrate model organism Caenorhabditis elegans. HD exposure led to much stronger beneficial locomotion effects in wild type worms compared to HT in the same concentration. Consistent to this finding, in OW13 worms, a PD-model characterized by &alpha, synuclein expression in muscles, HD exhibited a significant higher effect on &alpha, synuclein accumulation and swim performance than HT, an effect partly confirmed also in swim assays with the UA44 strain, which features &alpha, synuclein expression in DA-neurons. Interestingly, beneficial effects of HD and HT treatment with similar strength were detected in the lifespan and autofluorescence of wild-type nematodes, in the neuronal health of UA44 worms as well as in the locomotion of rotenone-induced PD-model. Thus, the hypothesis that HD features higher healthspan-promoting abilities than HT was at least partly confirmed. Our study demonstrates that HD polyphenolic extract treatment has the potential to partly prevent or even treat ageing-related neurodegenerative diseases and ageing itself. Future investigations including mammalian models and human clinical trials are needed to uncover the full potential of these olive compounds.
- Published
- 2020
- Full Text
- View/download PDF
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