SEARCHNARRATIVE_REVIEWbiomedical research, antioxidants

narrative_review·biomedical research, antioxidants, nutrition, clinical nutrition, preclinical research·PMC10475008

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

Archives of Toxicology · 7 authors, 4 centres

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This narrative review discusses the dual role of reactive oxygen species (ROS) in physiology and pathology, and how oxidative stress is a common mechanism in many chronic diseases and aging.

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This narrative review synthesizes literature on the chemistry and biological roles of reactive oxygen and nitrogen species (ROS/RNS). It details how oxidative eustress (physiological levels) regulates signaling, while oxidative stress (elevated levels) causes damage to DNA, proteins, and lipids, contributing to the pathology of numerous chronic diseases including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The review outlines the body's multi-line antioxidant defense system, comprising enzymes like superoxide dismutase and low-molecular-weight antioxidants such as vitamins C and E. It notes that while megadose vitamin supplementation has proven ineffective in clinical studies, some compounds like flavonoids show promise by boosting endogenous antioxidant systems.

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narrative_review

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biomedical research

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ORIGINAL PAPER

PMC10475008

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

Archives of Toxicology

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

CITATION EXPORT

Klaudia Jomova, Renata Raptova, Suliman Y. Alomar et al.. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Archives of Toxicology. (2023). https://doi.org/10.1007/s00204-023-03562-9

AUTHORS

7 · 4 CENTRES

Klaudia Jomova, Renata Raptova, Suliman Y. Alomar, Saleh H. Alwasel, Eugenie Nepovimova, Kamil Kuca, Marian Valko

1grid.411883.70000 0001 0673 7167Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University in Nitra, Nitra, 949 74 Slovakia
2grid.440789.60000 0001 2226 7046Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, 812 37 Slovakia
3grid.56302.320000 0004 1773 5396Zoology Department, College of Science, King Saud University, 11451 Riyadh, Saudi Arabia
4grid.4842.a0000 0000 9258 5931Department of Chemistry, Faculty of Sciences, University of Hradec Kralove, 50005 Hradec Kralove, Czech Republic