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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Role of Glutathione in Cancer: From Mechanisms to Therapies

Biomolecules, Journal Year: 2020, Volume and Issue: 10(10), P. 1429 - 1429

Published: Oct. 9, 2020

Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, xenobiotics. Recent studies have highlighted importance GSH key signal transduction reactions controller cell differentiation, proliferation, apoptosis, ferroptosis immune function. Molecular changes antioxidant system disturbances homeostasis been implicated tumor initiation, progression, treatment response. Hence, has both protective pathogenic roles. Although healthy crucial for removal detoxification carcinogens, elevated levels are associated with progression increased resistance to chemotherapeutic drugs. Recently, several novel therapies developed target tumors means response decreased drug resistance. In this comprehensive review we explore mechanisms functionalities different therapeutic approaches that either directly, indirectly or use GSH-based prodrugs. Consideration also given computational methods used describe related processes silico testing effects.

Language: Английский

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An update on β-sitosterol: A potential herbal nutraceutical for diabetic management

Biomedicine & Pharmacotherapy, Journal Year: 2020, Volume and Issue: 131, P. 110702 - 110702

Published: Aug. 31, 2020

Phytosterols are bioactive compounds that naturally present in plant cell membranes with chemical structure similar to the mammalian cell- derived cholesterol. They highly lipid-rich foods such as nuts, seed, legumes and olive oil. Among various phytosterols, β-sitosterol (SIT) is major compound, found plentiful plants. It has been evidenced many in-vitro in-vivo studies SIT possesses biological actions anxiolytic & sedative effects, analgesic, immunomodulatory, antimicrobial, anticancer, anti – inflammatory, lipid lowering effect, hepatoprotective, protective effect against NAFLD respiratory diseases, wound healing antioxidant anti-diabetic activities. In this review, order compile sources, characterization, biosynthesis, pharmacokinetics, activities of SIT, classical online-literature were studied which includes electronic search (Sci Finder, Pubmed, Google Scholar, Scopus, Web Science etc) books on photochemistry. The experimental gives a clear evidence potential phytosterol can be used supplements fight life threatening diseases. High classifies it notable drug future. Therefore, immense researches regarding its action at molecular level diseases humans endorsed.

Language: Английский

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Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 13

Published: March 9, 2020

Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder characterized by chronic hyperglycemia and an inadequate response to circulatory insulin peripheral tissues resulting in resistance. Insulin resistance has a complex pathophysiology, it contributed multiple factors including oxidative stress. Oxidative stress refers imbalance between free radical production antioxidant system leading reduction of sensitivity contributing development T2DM via several molecular mechanisms. In this review, we present mechanisms which milieu contributes pathophysiology mellitus.

Language: Английский

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An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 5938 - 5938

Published: May 25, 2022

Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress several neurodegenerative disorders. This review intends to summarize some findings that correlate overproduction reactive oxygen species pathophysiology Alzheimer’s disease, Parkinson’s Huntington’s and amyotrophic lateral sclerosis. was also noted modify inflammatory response. Even though oxidative neuroinflammation are two totally different pathological events, they affect one another. Nonetheless, there still mechanisms need be understood regarding onset diseases order develop efficient therapies. As antioxidants means alter slow down symptoms these most common antioxidants, enzymatic as well non-enzymatic, have mentioned this paper therapeutic options for discussed

Language: Английский

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Exercise-induced oxidative stress: Friend or foe?

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2020, Volume and Issue: 9(5), P. 415 - 425

Published: May 4, 2020

The first report demonstrating that prolonged endurance exercise promotes oxidative stress in humans was published more than 4 decades ago. Since this discovery, many ensuing investigations have corroborated the fact muscular increases production of reactive oxygen species (ROS) and results numerous tissues including blood skeletal muscles. Although several may contribute to exercise-induced ROS production, it is predicted contractions stimulate active muscle fibers a primary source during exercise. This contraction-induced generation associated with (1) oxidant damage (e.g., increased protein oxidation lipid peroxidation), (2) accelerated fatigue, (3) activation biochemical signaling pathways adaptation contracting fibers. While our understanding has advanced rapidly last decades, questions remain about whether are beneficial or harmful health. review addresses issue by discussing site(s) detailing health consequences production.

Language: Английский

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Beneficial Role of Phytochemicals on Oxidative Stress and Age-Related Diseases

BioMed Research International, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 16

Published: April 7, 2019

Aging is related to a number of functional and morphological changes leading progressive decline the biological functions an organism. Reactive Oxygen Species (ROS), released by several endogenous exogenous processes, may cause important oxidative damage DNA, proteins, lipids, cellular dysfunctions. The imbalance between ROS production antioxidant defenses brings stress conditions and, accumulation ROS, aging-associated diseases. purpose this review provide overview most relevant data reported in literature on natural compounds, mainly phytochemicals, with activity their potential protective effects age-related diseases such as metabolic syndrome, diabetes, cardiovascular disease, cancer, neurodegenerative chronic inflammation, possibly lower side effects, when compared other drugs.

Language: Английский

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Oxidative Stress in Cardiovascular Diseases

Antioxidants, Journal Year: 2020, Volume and Issue: 9(9), P. 864 - 864

Published: Sept. 14, 2020

Reactive oxygen species (ROS) are subcellular messengers in signal transductions pathways with both beneficial and deleterious roles. ROS generated as a by-product of mitochondrial respiration or metabolism by specific enzymes such superoxide dismutases, glutathione peroxidase, catalase, peroxiredoxins, myeloperoxidases. Under physiological conditions, the low levels production equivalent to their detoxification, playing major role cellular signaling function. In pathological situations, particularly atherosclerosis hypertension, release exceeds endogenous antioxidant capacity, leading cell death. At cardiovascular levels, oxidative stress is highly implicated myocardial infarction, ischemia/reperfusion, heart failure. Here, we will first detail vessels. Indeed, able regulate multiple functions, proliferation, migration, Second, investigate implication diseases. Then, focus on produced NAPDH oxidase during endothelial dysfunction. Given importance at level, therapies could be real benefit. last part this review, new therapeutic strategies potentially involved protection currently under study.

Language: Английский

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Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2345 - 2345

Published: Nov. 27, 2022

Organisms are continually exposed to exogenous and endogenous sources of reactive oxygen species (ROS) other oxidants that have both beneficial deleterious effects on the cell. ROS important roles in a wide range physiological processes; however, high levels associated with oxidative stress disease progression. Oxidative has been implicated nearly all major human diseases, from neurogenerative diseases neuropsychiatric disorders cardiovascular disease, diabetes, cancer. Antioxidant defence systems evolved as means protection against stress, transcription factor Nrf2 key regulator. is responsible for regulating an extensive panel antioxidant enzymes involved detoxification elimination extensively studied contexts. This review aims provide reader general overview Nrf2, including basic mechanisms activation regulation, implications various diseases.

Language: Английский

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Beneficial and Detrimental Effects of Reactive Oxygen Species on Lifespan: A Comprehensive Review of Comparative and Experimental Studies

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Feb. 11, 2021

Aging is the greatest risk factor for a multitude of diseases including cardiovascular disease, neurodegeneration and cancer. Despite decades research dedicated to understanding aging, mechanisms underlying aging process remain incompletely understood. The widely-accepted free radical theory (FRTA) proposes that accumulation oxidative damage caused by reactive oxygen species (ROS) one primary causes aging. To define relationship between ROS there have been two main approaches: comparative studies measure outcomes related across with different lifespans, experimental modulate levels within single using either genetic or pharmacologic approach. Comparative shown are inversely correlated lifespan. While these in general support FRTA, this type experiment can only demonstrate correlation, not causation. Experimental involving manipulation model organisms generally interventions increase tend decrease lifespan, while However, also multiple examples which opposite observed: increasing results extended longevity, decreasing shortened contradict predictions experiments performed very limited number species, all relatively short Overall, data suggest lifespan complex, both beneficial detrimental effects on longevity depending conditions. Accordingly, difficult generalize tree life.

Language: Английский

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