Pleiotropic roles of melatonin against oxidative stress mediated tissue injury in the gastrointestinal tract: An overview

2019 ◽  
Vol 2 (2) ◽  
pp. 158-184 ◽  
Author(s):  
Palash K Pal ◽  
Bharati Bhattacharjee ◽  
Aindrila Chattopadhyay ◽  
Debasish Bandyopadhyay
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Gi Tract ◽  
Pathological Conditions

The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress.  In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.

Abstract MP58: Tissue And Sex Specific Effects Of Gstm1 Deletion In Mouse Models

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yves Wang ◽  
Nhu Nguyen ◽  
Keith Nehrke ◽  
Paul S Brookes ◽  
Thu H Le
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Iri Model ◽  
Increased Risk ◽  
Study Gene Expression

The glutathione S-transferase ( Gst ) gene family encodes antioxidant enzymes. In humans, a common null allele deletion variant of GST μ-1 ( GSTM1 ) is highly prevalent across populations and is associated with increased risk and progression of various diseases. Using a Gstm1 knockout (KO) mouse model, we previously showed that KO mice with angiotensin II-induced hypertension (HTN) have increased kidney injury compared to wild-type (WT) controls, mediated by elevated oxidative stress. In the same mouse model, we have recently reported that in a Langendorff-perfused cardiac ischemia-reperfusion injury (IRI) model, where damage is also mediated by oxidative stress, male KO hearts are protected while females are not. Here, we investigated the molecular mechanisms for this difference in male hearts. WT and KO mice of both sexes were studied at 12-20 weeks of age. Hearts were snap frozen at baseline and after 25 min of global ischemia, and kidneys were collected at baseline and 4 weeks following HTN induction. A panel of 18 Gst genes were probed by qPCR from baseline hearts and kidneys of both sexes. Global metabolites were assayed using Metabolon, Inc. from hearts of both sexes and kidneys of males, at both baseline and diseased states. Analysis by qPCR (n = 3/group) showed that male, but not female, KO hearts had upregulation of other Gst s. In contrast, no significant differences between were found in male kidneys. Metabolomics (n = 6/group) detected 695 metabolites in hearts and 926 in kidneys. There were increases in several metabolites in KO vs. WT hearts including those with antioxidant properties. Notably, increases in carnosine and anserine were observed in KO male hearts but not in female hearts, while that of other antioxidant-related metabolites were observed in hearts of both sexes, but not in kidneys. HTN induced significant increases in metabolites in KO vs. WT kidneys in the pathways related to and linking methionine, cysteine, and glutathione, which were not observed in hearts. In this study, gene expression and metabolites suggest that the mechanisms compensating for the loss of GSTM1 are both tissue and sex specific. The resulting differences in antioxidant enzymes and metabolites may explain the unexpected protection for male Gstm1 KO hearts in IRI.

scholarly journals Edaravone Ameliorates Depressive and Anxiety-like Behaviors via Sirt1/Nrf2/HO-1/Gpx4 Pathway

2021 ◽  
Author(s):  
Ruozhi Dang ◽  
Mingyang Wang ◽  
Xinhui Li ◽  
Haiyang Wang ◽  
Lanxiang Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Forced Swim Test ◽  
Preference Test ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Nissl Staining

Abstract Background: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms.Methods: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. C57BL/6J mice were intraperitoneally injected with EDA or Vehicle daily for 10 days. Behaviors tests were then carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, measurement of MDA, SOD, GSH and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi(GPX4)-EGFP infusion.Results: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. Additionally, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage and energy metabolism in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors.Conclusion: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

Enterochromaffin cells as the source of melatonin: key findings and functional relevance in mammals

2019 ◽  
Vol 2 (4) ◽  
pp. 61-82
Author(s):  
Palash K. Pal ◽  
Swaimanti Sarkar ◽  
Aindrila Chattopadhyay ◽  
Dunxian X Tan ◽  
Debasish Bandyopadhyay
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Critical Role ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Protective Effects ◽  
Gi Tract ◽  
Food Residue ◽  
Ec Cells ◽  
Functional Relevance

The enteroendocrine cells in gastrointestinal (GI) tract synthesize more than thirty hormones in mammals. Among these cells, the enterochromaffin (EC) cells are probably the most important one due to the fact that they produce melatonin. The rate-limiting enzymes for melatonin synthesis including arylalkylamine-N-acetyltransferase (AANAT, currently the SNAT) and hydroxyindole-O-methyltransferase (HIOMT, currently the ASMT) have been identified in EC cells and this has confirmed the local melatonin production in GI tract by these cells. EC cells play a critical role in regulation of gastrointestinal physiology, particularly, in protection of the GI tract from free radical attack and inflammatory reaction. GI tract is the major site exposed to the oxidative stress and inflammation because of the food residue metabolism and the presence of trillions of microbes including the pathological bacteria. Thus, it requires strong protection. Melatonin synthesized by the EC cells provides the onsite protection in GI tract since this molecule is the potent free radical scavenger and effective ant-inflammatory agent. In this review we summarize the available information regarding the structural and functional variability of the EC cells as well as their pathophysiological roles in the GI tract. The focus is given to the protective effects of melatonin produced by the EC cells on the oxidative stress, inflammation and microbiota balance in GI tract. 

scholarly journals S-allyl Cysteine, a Garlic Compound, Produces an Antidepressant-Like Effect and Exhibits Antioxidant Properties in Mice

2020 ◽  
Vol 10 (9) ◽  
pp. 592
Author(s):  
Elizabeth Ruiz-Sánchez ◽  
José Pedraza-Chaverri ◽  
Omar N. Medina-Campos ◽  
Perla D. Maldonado ◽  
Patricia Rojas
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Forced Swim Test ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Antidepressant Effect ◽  
Radical Scavenger ◽  
Oxidative Stress Markers ◽  
Sod Activity ◽  
Stress Markers

Depression is a psychiatric disorder, and oxidative stress is a significant mechanism of damage in this mood disorder. It is characterized by an enhancement of oxidative stress markers and low concentrations of endogenous antioxidants, or antioxidants enzymes. This suggests that antioxidants could have an antidepressant effect. S-allyl cysteine (SAC) is a compound with antioxidant action or free radical scavenger capacity. The purpose of the current research was to evaluate the antidepressant-like effect as well as the antioxidant role of SAC on a preclinical test, using the Porsolt forced swim test (FST). SAC (30, 70, 120, or 250 mg/kg, ip) was administered to male BALB/c mice daily for 17 days, followed by the FST at day 18. Oxidative stress markers (reactive oxygen species, superoxide production, lipid peroxidation, and antioxidant enzymes activities) were analyzed in the midbrain, prefrontal cortex, and hippocampus. SAC (120 mg/kg) attenuated the immobility scores (44%) in the FST, and protection was unrelated to changes in locomotor activity. This antidepressant-like effect was related to decreased oxidative stress, as indicated by lipid peroxidation and manganese-superoxide dismutase (Mn-SOD) activity in the hippocampus. SAC exerts an antidepressant-like effect that correlated, in part, with preventing oxidative damage in hippocampus.

Melatonin attenuates chemical-induced cardiotoxicity

2020 ◽  
pp. 096032712095941
Author(s):  
S Zare ◽  
FS Heydari ◽  
AW Hayes ◽  
RJ Reiter ◽  
MR Zirak ◽  
...  
Keyword(s):  
Free Radicals ◽  
Molecular Mechanisms ◽  
Cardiovascular Health ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Critical Role ◽  
Free Radical Scavenger ◽  
Environmental Chemicals ◽  
Model Systems ◽  
Radical Scavenger

Environmental chemicals and drugs can induce cardiotoxicity, mainly by generating free radicals. Reactive oxygen species play a critical role in the pathogenesis of cardiac tissue injury. This highlights a need for prevention of cardiotoxicity by scavenging free radicals. Melatonin has been shown to act as a protector against various conditions in which free radicals cause molecular and tissue injury. Some of the mechanisms by which melatonin operates as a free radical scavenger and antioxidant have been identified. The importance of endogenous melatonin in cardiovascular health and the benefits of melatonin supplementation in different cardiac pathophysiological disorders have been shown in a variety of model systems. Melatonin continues to attract attention for its potential therapeutic value for cardiovascular toxicity. The therapeutic potential of melatonin in treatment of cardiotoxicities caused by various chemicals along with suggested molecular mechanisms of action for melatonin is reviewed.

Protective effect of vitamin E and epicatechin against nicotine-induced oxidative stress in rats

2012 ◽  
Vol 29 (2) ◽  
pp. 202-208 ◽  
Author(s):  
Abdulrahman L Al-Malki ◽  
Said S Moselhy
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Combined Treatment ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Individual Treatment ◽  
Antioxidant Vitamin ◽  
Radical Scavenger ◽  
Pharmacologically Active ◽  
Chemopreventive Activity

Nicotine is a major pharmacologically active and addictive component of tobacco smoke, which is regarded to be a primary risk factor in the development of cardiovascular and pulmonary diseases. Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels of this compound are found in tea, apples and chocolate. It has been reported that tea extracts and/or its constituents have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities. Vitamin E is a major lipid-soluble antioxidant vitamin and free radical scavenger, presents as an integral component of cellular membranes and has important biological functions. The primary mechanism by which vitamin E is proposed to prevent cancer is through their antioxidant properties. The goal of this study is to evaluate the effect of epicatechin alone or combined with vitamin E in inhibiting the oxidative stress induced by nicotine in rats. Results obtained indicated that there was a significant elevation in the levels of malondialdhyde (MDA) in nicotine injected rats. The combined treatment (epicatechin + Vit E) group showed a potential reduction of these parameters more than individual treatment. The activities of superoxide dismutase, catalase and glutathione peroxidase were found significantly higher in combined treated than untreated rats. In nicotine group, a negative significant correlation between reduced glutathione and MDA ( r = −0.92) was observed. In conclusion, these results suggested that the supplementation of diet with epicatechin and vitamin E provided antioxidant defense with strong chemopreventive activity against nicotine-induced carcinogenesis.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

Investigation of Antioxidant Activity of Pomegranate Juices by Means of Electron Paramagnetic Resonance and UV-Vis Spectroscopy

2015 ◽  
Vol 98 (4) ◽  
pp. 866-870 ◽  
Author(s):  
Violetta Kozik ◽  
Krystyna Jarzembek ◽  
Agnieszka Jędrzejowska ◽  
Andrzej Bąk ◽  
Justyna Polak ◽  
...  
Keyword(s):  
Electron Paramagnetic Resonance ◽  
Free Radical ◽  
Epr Spectroscopy ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Pomegranate Juice ◽  
Radical Scavenger ◽  
Paramagnetic Resonance ◽  
Vis Spectroscopy ◽  
Electron Paramagnetic

Abstract Pomegranate fruit (Punica granatum L.) is a source of numerous phenolic compounds, and it contains flavonoids such as anthocyanins, anthocyanidins, cyanidins, catechins and other complexes of flavonoids, ellagitannins, and hydrolyzed tannins. Pomegranate juice shows antioxidant, antiproliferative, and anti-atherosclerotic properties. The antioxidant capacity (TEAC) of the pomegranate juices was measured using electron paramagnetic resonance (EPR) spectroscopy and 1,1-diphenyl-2-picrylhydrazyl (DPPH•) as a source of free radicals, and the total phenolic (TP) content was measured using UV-Vis spectroscopy. All the examined pomegranate juices exhibited relatively high antioxidant properties. The TEAC values determined by means of EPR spectroscopy using Trolox (TE) as a free radical scavenger were in the range of 463.12 to 1911.91 μmol TE/100 mL juice. The TP content measured by the Folin-Ciocalteu method, using gallic acid (GA) as a free radical scavenger, widely varied in the investigated pomegranate juice samples and ranged from 1673.62 to 5263.87 mg GA/1 L juice. The strongest antioxidant properties were observed with the fresh pomegranate juices obtained from the fruits originating from Israel, Lebanon, and Azerbaijan. Correlation analysis of numerical data obtained by means of EPR spectroscopy (TEAC) and UV-Vis spectroscopy (TP) gave correlation coefficient (r) = 0.90 and determination coefficient (r2) = 0.81 (P <0.05).

scholarly journals Potential benefits of melatonin in organ transplantation: a review

2016 ◽  
Vol 229 (3) ◽  
pp. R129-R146 ◽  
Author(s):  
Eduardo Esteban-Zubero ◽  
Francisco Agustín García-Gil ◽  
Laura López-Pingarrón ◽  
Moisés Alejandro Alatorre-Jiménez ◽  
Pablo Iñigo-Gil ◽  
...  
Keyword(s):  
Free Radical ◽  
Organ Transplantation ◽  
Graft Rejection ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Defense System ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Therapeutic Tool ◽  
Term Survival

Organ transplantation is a useful therapeutic tool for patients with end-stage organ failure; however, graft rejection is a major obstacle in terms of a successful treatment. Rejection is usually a consequence of a complex immunological and nonimmunological antigen-independent cascade of events, including free radical-mediated ischemia-reperfusion injury (IRI). To reduce the frequency of this outcome, continuing improvements in the efficacy of antirejection drugs are a top priority to enhance the long-term survival of transplant recipients. Melatonin (N-acetyl-5-methoxytryptamine) is a powerful antioxidant and ant-inflammatory agent synthesized from the essential amino acid l-tryptophan; it is produced by the pineal gland as well as by many other organs including ovary, testes, bone marrow, gut, placenta, and liver. Melatonin has proven to be a potentially useful therapeutic tool in the reduction of graft rejection. Its benefits are based on its direct actions as a free radical scavenger as well as its indirect antioxidative actions in the stimulation of the cellular antioxidant defense system. Moreover, it has significant anti-inflammatory activity. Melatonin has been found to improve the beneficial effects of preservation fluids when they are enriched with the indoleamine. This article reviews the experimental evidence that melatonin is useful in reducing graft failure, especially in cardiac, bone, otolaryngology, ovarian, testicular, lung, pancreas, kidney, and liver transplantation.

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