Redox Experimental Medicine最新文献

{"title":"Glutathione in cancer progression and chemoresistance: an update","authors":"G. E. Valenti, B. Tasso, N. Traverso, C. Domenicotti, B. Marengo","doi":"10.1530/rem-22-0023","DOIUrl":"https://doi.org/10.1530/rem-22-0023","url":null,"abstract":"Glutathione is one of the most important components of the cellular antioxidant system and it is able to exert several pleiotropic functions influencing cell growth, proliferation, adaptation and death. It has been demonstrated that changes in glutathione levels underlie the pathogenesis of many human diseases, including cancer. In detail, although on one hand glutathione homeostasis plays a protective role from the onset of cancer, on the other, it is involved in cancer progression and in therapy resistance. \u0000\u0000Objective: In this review, after a brief report on the physiological role of glutathione, we have focused the attention on its role in cancer and refractoriness to anticancer therapy giving an update on the preclinical and clinical studies relied on the compounds targeting glutathione system.\u0000\u0000Conclusions and significance: Based on these considerations, a deeper knowledge of glutathione-dependent network can be crucial to identify new strategies for preventing and/or curing cancer. \u0000","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114345441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterotoxic potential of dietary cholesterol autoxidation products","authors":"Noemi Iaia, Federico Canzoneri, Ginevra Rosso, R. Menta, F. Biasi","doi":"10.1530/rem-22-0022","DOIUrl":"https://doi.org/10.1530/rem-22-0022","url":null,"abstract":"In both Western and Westernized diets, together with a relatively high amount of cholesterol, a variable amount of its oxidized metabolites, oxysterols, are consistently taken up. These oxysterols, mostly of non-enzymatic origin, are produced during sterol autoxidation in foodstuff manufacturing and storage. Objective: analysis of the potential enterotoxic effects of all main oxysterols of non-enzymatic origin so far identified in a variety of foods. Experimental plan: differentiated human intestinal cell monolayers (CaCo-2) were incubated up to 48 h in the presence or absence of 0.5, 1 or 5 µM with one out of seven non-enzymatic oxysterols, prior verification of a minimal irreversible cell damage within the chosen concentration range. Results: all tested oxysterols were in vitro proven to exert damaging effects on cell monolayers. The inflammatory interleukin-8 and monocyte chemotactic protein-1 were mostly up-regulated by 7-ketocholesterol and 7β-hydroxycholesterol, respectively, then to a lower extent by 5α,6α-epoxycholesterol, 7α-hydroxycholesterol and 5β,6β-epoxycholesterol. 7-Ketocholesterol and 7β-hydroxycholesterol also appeared to be the most effective in impairing claudin-1, occludin and E-cadherin proteins, followed by 25-hydroxycholesterol and triol. Conclusions: the oxysterols consistently deriving by food autoxidation were tested: they potentially impaired the intestinal epithelial barrier integrity and triggered an inflammatory response already within the 0.5-5 µM concentrations easily reachable in a single Western meal. Significance: this comprehensive analysis focused on the potential impairment of intestinal barrier by the main dietary non-enzymatic oxysterols, should guide further nutrition research aiming at defining a threshold amount of these cholesterol derivatives in order not to derange the physiological gut-brain axis.\u0000","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126135644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemicals to regulate oxidative and electrophilic stress through Nrf2 activation","authors":"Y. Abiko, A. Toriba, Y. Kumagai","doi":"10.1530/rem-22-0021","DOIUrl":"https://doi.org/10.1530/rem-22-0021","url":null,"abstract":"Intake of a variety of vegetables and fruit is found to be effective in promoting health; one of the reasons why is activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a basic leucine zipper protein. Nrf2 is activated by chemical modification of Kelch-like ECH-associated protein 1 (Keap1), a negative regulator for this transcription factor, and specific phosphorylation of Nrf2, resulting in upregulation of its downstream gene products for antioxidant proteins, phase-II xenobiotic metabolizing enzymes, and phase-III transporters. This type of activation plays a role in adaptive response and protection against oxidative and electrophilic stress. Multiple phytochemicals, such as curcumin, sulforaphane, and (E)-2-alkenals have been identified as Nrf2 activators and may reduce adverse health effects of oxidants and electrophiles. In this review, we introduce plant components that are known as Nrf2 activators and associated phytochemical-mediated reduction of risk from chemicals which cause oxidative and electrophilic stress. We also discuss capture and inactivation of methylmercury, an electrophile, by sulfane sulfur atoms contained in garlic.\u0000","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"140 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131656424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox medicine in viral infections: focus on AIDS and COVID-19","authors":"C. Mas-Bargues, C. Borrás, J. Viña","doi":"10.1530/rem-22-0017","DOIUrl":"https://doi.org/10.1530/rem-22-0017","url":null,"abstract":"Despite the great progress and advancements in scientific knowledge, technology, and medicine, viral infections continue to put human health in trouble. Both acquired immunodeficiency syndrome (AIDS) and coronavirus disease-2019 (COVID-19), caused by HIV and SARS-CoV-2, two RNA viruses responsible for global pandemics respectively, have poor outcomes associated with increased oxidative stress, systemic inflammation, and immunopathology. Here, we have collected the current knowledge linking both viral infections, focusing on the role of oxidative stress and the redox balance. Furthermore, we provide information on some redox-active compounds, such as vitamins, thiol-based agents, and polyphenols, and their possible beneficial effects on both diseases. Thus, in this review, we aim to highlight the importance and impact of nutritional strategies to strengthen our immune system, especially to increase the effectiveness of pharmacological treatments, or when there are no effective treatments.","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133060161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HESPERETIN ATTENUATES TEICOPLANIN-INDUCED ACUTE KIDNEY INJURY BY MITIGATING OXIDATIVE STRESS AND INFLAMMATION IN WISTAR RAT","authors":"E. Olayinka, Toluwalase Oreofe Oni, A. Olajide, B. Ajayi, S. Kehinde","doi":"10.1530/rem-22-0018","DOIUrl":"https://doi.org/10.1530/rem-22-0018","url":null,"abstract":"Objectives: Renal failure has been reported in patients treated with Teicoplanin, a widely used antibiotic. Hesperetin, a flavonoid in citrus fruits, has been reported to possess nephro-protective effects. This study investigated the protective effect of hesperetin on teicoplanin-induced nephrotoxicity in rats.\u0000\u0000Methods: Male wistar rats (n=32, 144-180 g) were grouped into 4 groups of 8 rats each. The control, group 1 received water, group 2 received 50 mg/kg of hesperetin orally, group 3 received 10 mg/kg of teicoplanin intraperitoneally and group 4 received 50 mg/kg of hesperetin and 10 mg/kg of teicoplanin. Administration was done for 21 days. Rats were sacrificed 24 hours after the last administration, the kidney was excised and used for biochemical assays. \u0000\u0000Results: Administration of teicoplanin resulted in kidney injury that was characterized by significant increase in plasma urea and creatinine level relative to control group (p<0.05). Additionally, significant increase in biomarkers of inflammation (NO, MPO, TNF-α) and lipid peroxidation (malondialdehyde) of teicoplanin-treated rats were observed when compared with the control group. Furthermore, altered antioxidants status was observed following teicoplanin treatment. Activities of enzymic antioxidants (SOD, CAT, GPx, GST) and concentration of non-enzymic antioxidants (GSH and Ascorbic acid) were downregulated. In comparison to the teicoplanin-treated group, the administration of Hesperetin with teicoplanin significantly reduced all changes in the markers of kidney injury, inflammation, and oxidative stress. Histopathological examination revealed that rats given TEIC showed increased glomerular size and considerable hydropic changes in the proximal convoluted tubules, whereas rats given HESP and TEIC showed only mildly enhanced glomerular size and hydropic modifications. \u0000\u0000Conclusion: Hesperetin preserved the histo-architecture of the kidney. From this study, hesperetin offered a protective effect against teicoplanin-induced nephrotoxicity in rats.","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128984928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of plasma and tissue distribution of 27-hydroxycholesterol after a single oral administration in a mouse model","authors":"Valerio Leoni, C. Caccia, Federica Vitarelli, A. Civra, D. Lembo, R. Cavalli, M. Adami, D. Risso, R. Menta, G. Poli","doi":"10.1530/rem-22-0020","DOIUrl":"https://doi.org/10.1530/rem-22-0020","url":null,"abstract":"The side chain 27-hydroxycholesterol (27OHC) has been reported to inhibit the replication of several pathogen viruses, including Herpes Simplex virus, Rhinovirus, Rotavirus and SARS-CoV-2, in in vitro and ex vivo models. Objective: in view of a future potential therapeutic use of 27-hydroxycholesterol 27OHC, a pilot pharmacokinetic study was set up. Methods: this active substance was complexed with 2-hydroxypropyl-β-cyclodextrin and orally administered in a single dose to CD1 male mice, then evaluating its recovery in plasma and a few tissues up to 24 h post-treatment. Results: the absorption of the oxysterol by the small intestine was moderate, due to its physicochemical properties, but still relevant and rapid, showing a peak 1 hour after supplementation and being almost completed 24 hours after treament. 27-Hydroxycholesterol 27OHC appeared to be a high hepatic extraction drug, possibly with an extrahepatic component contributing to the total clearance. Conclusions: following the oral 25 mg/kg dosing, plasma levels of 27-hydroxycholesterol 27OHC showed an average steady-state concentration similar to that inhibiting in vitro the replication of all the viruses tested so far. Significance: here reported are the first pharmacokinetic data relative to a natural oxysterol administered per os. Data that should contribute to further elucidate oxysterols pathophysiology and guide non-clinical studies aiming at investigating possible therapeutic use of 27OHC or its analogs.","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134498425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress leads to severe phenotypes in sepsis through activation of NLRP3-pyroptosis","authors":"J. Beltrán-García, R. Osca-Verdegal, J. García-Giménez, F. Pallardó","doi":"10.1530/rem-22-0006","DOIUrl":"https://doi.org/10.1530/rem-22-0006","url":null,"abstract":"Oxidative stress is an important contributor in sepsis, one of the most important causes of death in intensive care units. Even though sepsis pathogenesis remains obscure due to its heterogenicity and complexity, there is increasing evidence that oxidants and antioxidants play a key role in its onset and progression. Recent evidence suggests that pyroptosis is required for defense against bacterial infection, and it is active in several cell types during sepsis. One of the most relevant mediators of pyroptosis is the NLRP3 inflammasome, been the oxidative stress/NLRP3 signaling pathway one of the main upstream signals involved in its activation. So, it is of special relevance to clarify how oxidative stress and antioxidants can modulate pyroptosis signals and therefore decrease the deleterious effects that both oxidative stress and pyroptosis-related cytokines can induce in the tissues during sepsis. Recent studies evaluating several antioxidants are promising, but further trials are needed to confirm their potential role as agents to block NLRP3 and mitigate the exacerbated inflammasome-related responses during sepsis.","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115540874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox-sensitive DJ-1 protein: An insight into physiological roles, secretion, and therapeutic target","authors":"B. Dash, Yasuomi Urano, Yoshiro Saito, N. Noguchi","doi":"10.1530/rem-22-0007","DOIUrl":"https://doi.org/10.1530/rem-22-0007","url":null,"abstract":"The highly conserved DJ-1 protein fundamentally acts as a redox sensor conferring antioxidative cytoprotection under oxidative insults. DJ-1 preferentially undergoes oxidation at 106 cysteine residue (Cys106) under oxidative stress. Although initially identified as an oncogene, emerging evidence suggests the essential roles of DJ-1 in modulating numerous physiological processes involved in cellular growth, development, survival, and death. Compromised DJ-1 expression and function directly or indirectly trigger signaling cascades leading to pathophysiological conditions including neurodegeneration, cancer, stroke, and inflammatory diseases. Besides the intracellular functions, enhanced DJ-1 secretion into the extracellular fluid, including cerebrospinal fluid and blood, is related to Parkinson’s disease (PD) and cancer pathogenesis. Here we review the current knowledge regarding DJ-1’s roles as a ubiquitous cytoprotective protein controlling numerous signaling pathways, secretion, and therapeutic potentials.\u0000","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"115 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117260943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preconditioning hypoxia induces neuroprotection against oxidative stress.","authors":"Iván Millán, Marisol Corral-Debrisky, M. Vento, I. Torres-Cuevas","doi":"10.1530/rem-22-0011","DOIUrl":"https://doi.org/10.1530/rem-22-0011","url":null,"abstract":"Brain is an oxyregulator organ, however extremely vulnerable to oxygen. Both high and low oxygen concentrations generate free radicals and may cause oxidative stress and damage because of an insufficient response of the antioxidant system. Hypoxic preconditioning exerts neuroprotective effects and may be a protecting tool against oxygen fluctuations thus preventing neuronal damage in events such as ischemia, acute hypoxia, stroke, or traumatic brain injury, among others.\u0000\u0000This review aims to discuss the molecular mechanisms involved in the neuroprotective action of HP against oxidative stress and subsequently upon the brain under pro-oxidant conditions. Activation of the antioxidant defences represents the first line to neutralize oxidative stress and is characterized by low reactive oxygen species (ROS), reduced oxidative damage biomarkers, and increased level of reduced glutathione (GSH). These protective mechanisms decrease cell death activating anti-apoptotic signalling pathways and reducing neuroinflammation by the inactivation of microglia and astroglia cells. HP could be considered a new approach to reduce oxidative stress derived damage caused by a great variety of brain pathologies. Despite our intriguing findings, further experiments are needed for a better understanding of the molecular mechanisms involved in the neuroprotective actions of HP.\u0000","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126988733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mitochondria: a great boon to fight type 2 diabetes","authors":"Aranzazu M de Marañón, S. Rovira-Llopis, M. Rocha, V. M. Víctor","doi":"10.1530/rem-22-0012","DOIUrl":"https://doi.org/10.1530/rem-22-0012","url":null,"abstract":"Type 2 diabetes is a chronic metabolic disease characterised by the development of low-grade systemic inflammation, hyperglycaemia, and hyperlipidaemia. These pathogenic traits have a profound impact on mitochondrial function as the intermediary organelles between nutrients and energy production. Moreover, the mitochondrial quality control system is also altered and rendered defective by type 2 diabetes. These alterations entail the accumulation of defective mitochondria, which causes the diabetic background to deteriorate further. In this context, it is of paramount importance to improve mitochondrial function and ameliorate the consequences of mitochondrial dysfunction. This review assesses different treatments that target mitochondrial dysfunction as a way of treating type 2 diabetes. Lifestyle interventions and pharmacological treatments such as biguanides, thiazolidinediones, a-glucosidase inhibitors or SGLT2 inhibitors protect mitochondrial function; while novel mitochondria-targeted molecules including natural compounds, mitochondria-targeted antioxidants, inhibitors of mPTP opening, NO and H2S donors, and inhibitors of mitochondrial fission positively impact on mitochondrial function and its quality control mechanisms. Most of these therapeutic tools require more research, but they already show promising therapeutic mechanisms that improve type 2 diabetes and its cellular consequences.\u0000","PeriodicalId":310409,"journal":{"name":"Redox Experimental Medicine","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123953294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}