Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 97(10), P. 2499 - 2574

Published: Aug. 19, 2023

Abstract A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” characterized by low to mild levels oxidants involved in the regulation various biochemical transformations such carboxylation, hydroxylation, peroxidation, modulation signal transduction pathways Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related 2 (Nrf2) other processes. Increased ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result a harmful condition stress (“bad stress”). Although it widely accepted, that many chronic diseases are multifactorial origin, they share common denominator. Here we review importance mechanisms through which contributes pathological states an organism. Attention focused on chemistry ROS RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl nitric oxide, peroxynitrite), their role damage DNA, proteins, membrane lipids. Quantitative qualitative assessment biomarkers also discussed. Oxidative pathology cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s Parkinson’s Down syndrome), psychiatric (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, cancer), aging. The concerted action antioxidants ameliorate effect achieved antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), small molecular weight (vitamins C E, flavonoids, carotenoids, melatonin, ergothioneine, others). Perhaps one most effective vitamin first line defense against peroxidation promising approach appears be use flavonoids), showing weak prooxidant properties may boost cellular systems thus act preventive anticancer agents. Redox metal-based enzyme mimetic compounds potential pharmaceutical interventions sirtuins therapeutic targets for age-related anti-aging strategies

Language: Английский

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Melatonin Suppresses Ferroptosis Induced by High Glucose via Activation of the Nrf2/HO-1 Signaling Pathway in Type 2 Diabetic Osteoporosis

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 18

Published: Dec. 4, 2020

Ferroptosis is recently identified, an iron- and reactive oxygen species- (ROS-) dependent form of regulated cell death. This study was designed to determine the existence ferroptosis in pathogenesis type 2 diabetic osteoporosis confirm that melatonin can inhibit osteoblasts through activating Nrf2/HO-1 signaling pathway improve bone microstructure vivo vitro. We treated MC3T3-E1 cells with different concentrations (1, 10, or 100 μM) exposed them high glucose (25.5 mM) for 48 h Our data showed induce osteoblast cytotoxicity accumulation lipid peroxide, mitochondria show same morphology changes as erastin treatment group, expression ferroptosis-related proteins glutathione peroxidase 4 (GPX4) cystine-glutamate antiporter (SLC7A11) downregulated, but these effects were reversed by inhibitor ferrastatin-1 iron chelator deferoxamine (DFO). Furthermore, western blot real-time polymerase chain reaction used detect levels nuclear factor erythroid 2-related (Nrf2) heme oxygenase-1 (HO-1); osteogenic capacity evaluated alizarin red S staining osteoprotegerin, osteocalcin, alkaline phosphatase; results 1, μM melatonins significantly higher than after using Nrf2-SiRNA interference, therapeutic effect inhibited. also performed experiments a rat model two (10, 50 mg/kg). Dynamic histomorphometry micro-CT observe microstructure, GPX4 Nrf2 determined immunohistochemistry. Here, we first report induces via increased ROS/lipid peroxidation/glutathione depletion osteoporosis. More importantly, reduced level improved

Language: Английский

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Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives

Biomolecules, Journal Year: 2022, Volume and Issue: 12(9), P. 1227 - 1227

Published: Sept. 2, 2022

Diabetes mellitus (DM) is one of the most debilitating chronic diseases worldwide, with increased prevalence and incidence. In addition to its macrovascular damage, through microvascular complications, such as Diabetic Kidney Disease (DKD), DM further compounds quality life these patients. Considering DKD main cause end-stage renal disease (ESRD) in developed countries, extensive research currently investigating matrix pathophysiology. Hyperglycemia, inflammation oxidative stress (OS) are mechanisms behind this disease. By generating pro-inflammatory factors (e.g., IL-1,6,18, TNF-α, TGF-β, NF-κB, MCP-1, VCAM-1, ICAM-1) activation diverse pathways PKC, ROCK, AGE/RAGE, JAK-STAT), they promote a pro-oxidant state impairment antioxidant system (NRF2/KEAP1/ARE pathway) and, finally, alterations filtration unit. Hitherto, wide spectrum pre-clinical clinical studies shows beneficial use NRF2-inducing strategies, NRF2 activators Bardoxolone methyl, Curcumin, Sulforaphane their analogues), other natural properties treatment. However, limitations regarding lack larger trials, solubility or delivery hamper implementation for use. Therefore, review, we will discuss mechanisms, especially NRF2/KEAP1/ARE involvement, while highlighting potential therapeutic approaches that target via OS.

Language: Английский

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Melatonin attenuates LPS-induced pyroptosis in acute lung injury by inhibiting NLRP3-GSDMD pathway via activating Nrf2/HO-1 signaling axis

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 109, P. 108782 - 108782

Published: April 23, 2022

Language: Английский

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Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 8, 2023

Abstract The maintenance of iron homeostasis is essential for proper endocrine function. A growing body evidence suggests that imbalance a key factor in the development several diseases. Nowadays, ferroptosis, an iron-dependent form regulated cell death, has become increasingly recognized as important process to mediate pathogenesis and progression type 2 diabetes mellitus (T2DM). It been shown ferroptosis pancreas β cells leads decreased insulin secretion; liver, fat, muscle induces resistance. Understanding mechanisms concerning regulation metabolism T2DM may lead improved disease management. In this review, we summarized connection between metabolic pathways molecular T2DM. Additionally, discuss potential targets treating analysis current limitations future directions these novel treatment targets.

Language: Английский

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Withania somnifera Ameliorates Doxorubicin-Induced Nephrotoxicity and Potentiates Its Therapeutic Efficacy Targeting SIRT1/Nrf2, Oxidative Stress, Inflammation, and Apoptosis

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 248 - 248

Published: Feb. 12, 2025

Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, anticancer activities. This study investigates the preventative benefits of standardized WIT extract against DOX-induced renal damage in vivo. We also investigate synergistic effects combining DOX to improve efficacy breast cancer cells (MCF7-ADR). Methods: employed an animal model where rats were administered 300 mg/kg/day orally duration 14 days. Rats received injections at dose 5 mg/kg, total 15 mg, on 6th, 8th, 10th Results: Present results revealed that reduced increase levels blood urea creatinine activity kidney injury molecule-1. tissue damage, oxidative stress, pro-inflammatory markers. alleviated nuclear factor erythroid 2-related 2, heme oxygenase-1, sirtuin 1 tissues. modulated factor-κB decreased apoptotic indicators. Furthermore, improves DOX's capacity kill drug-resistant MCF7-ADR by arresting cell cycle promoting apoptosis. Chemical analysis root 34 distinct compounds, alkaloids, withanolides, flavanones, fatty acids. Conclusions: These constituents synergistically contribute WIT's anti-apoptotic properties. In addition, they confirm ability reduce systemic while improving treatment efficacy.

Language: Английский

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Melatonin as a potential modulator of Nrf2

Fundamental and Clinical Pharmacology, Journal Year: 2019, Volume and Issue: 34(1), P. 11 - 19

Published: July 8, 2019

Abstract Nuclear factor erythroid 2‐related 2 (Nrf2) is considered as the sensor of oxidative stress, and main aim this signaling pathway to maintain physiological condition by induction redox balance. Also, exerts anti‐inflammatory effects via antioxidant response element. Oxidative stress a key in variety pathological conditions high level associated with damages lipids, proteins, genetic material, cell membrane. Multiple drugs have been developed order diminish stress. However, synthetic suffer from various drawbacks such cost side effects. On other hand, naturally occurring compounds are interest due their minimal valuable biological activities. Melatonin hormone pineal gland which found different plants. This compound has favorable therapeutic activities antioxidant, anti‐inflammatory, anti‐tumor, anti‐diabetic, cardioprotection. At present review, we demonstrate that Nrf2 explains some melatonin.

Language: Английский

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Pharmacological Protection against Ischemia-Reperfusion Injury by Regulating the Nrf2-Keap1-ARE Signaling Pathway

Antioxidants, Journal Year: 2021, Volume and Issue: 10(6), P. 823 - 823

Published: May 21, 2021

Ischemia/reperfusion (I/R) injury is associated with substantial clinical implications, including a wide range of organs such as the brain, kidneys, lungs, heart, and many others. I/R (IRI) occurs due to tissue following reestablishment blood supply ischemic tissues, leading enhanced aseptic inflammation stimulation oxidative stress via reactive oxygen nitrogen species (ROS/RNS). Since ROS causes membrane lipids' peroxidation, triggers loss integrity, denaturation proteins, DNA damage, cell death, plays critical part in pathogenesis. Therefore, regulation could be promising therapeutic strategy for IRI. In this context, Nrf2 (NF-E2-related factor 2) transcription that regulates expression several factors involved cellular defense against inflammation, heme oxygenase-1 (HO-1). Numerous studies have shown potential role Nrf2/HO-1 pathway IRI; thus, we will review molecular aspects Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE) signaling I/R, also highlight recent insights into targeting preventing

Language: Английский

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Melatonin: new insights on its therapeutic properties in diabetic complications

Diabetology & Metabolic Syndrome, Journal Year: 2020, Volume and Issue: 12(1)

Published: April 8, 2020

Diabetes and diabetic complications are considered as leading causes of both morbidity mortality in the world. Unfortunately, routine medical treatments used for affected patients possess undesirable side effects, including kidney liver damages well gastrointestinal adverse reactions. Therefore, exploring novel therapeutic strategies is a crucial issue. It has been recently shown that melatonin, main product pineal gland, despite its various pharmacological features anticancer, anti-aging, antioxidant anti-inflammatory exerts anti-diabetic properties through regulating cellular mechanisms. The aim present review to describe potential roles melatonin treatment diabetes complications.

Language: Английский

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Fucoxanthin Attenuates Oxidative Damage by Activating the Sirt1/Nrf2/HO-1 Signaling Pathway to Protect the Kidney from Ischemia-Reperfusion Injury

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 28

Published: Jan. 28, 2022

Oxidative stress is a key component of renal ischemia/reperfusion (I/R) injury. Fucoxanthin (Fx), marine carotenoid with enhanced antioxidant capacity, acts as ROS inhibitor in diseases such ischemic stroke and acute lung We hypothesized that fucoxanthin could attenuate I/R-induced oxidative damage. C57BL/6 mice (n = 30) were randomly assigned to sham, IR, IR + DMSO, Fx (25, 50, 100 mg/kg) groups. The I/R injury was induced by clamping the left kidney nephron tip mice. injected intraperitoneally 24 hours before surgery. Compared group, pretreatment significantly improved dysfunction tissue structural damage inhibited levels apoptosis. Consistent results observed HK-2 cells. Besides, we found resulted decreased expression Sirt1, Nrf2, HO-1, while upregulated HO-1. protective effects reversed EX527 (a selective Sirt1) or si-Sirt1. In conclusion, our study investigated effect against injury, underlying mechanism may be related activation Sirt1/Nrf2/HO-1 signaling pathway stress-induced

Language: Английский

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