Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(5), P. 1323 - 1367

Published: March 14, 2024

Abstract Reactive oxygen species (ROS) and reactive nitrogen (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production elimination is termed oxidative stress, critical factor common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic neurological disorders (Alzheimer’s Parkinson’s diseases), other disorders. To counteract the harmful effects ROS, organisms have evolved complex, three-line antioxidant defense system. The first-line mechanism most efficient involves enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). This line plays an irreplaceable role in dismutation radicals (O 2 ·− ) hydrogen peroxide (H O ). removal by SOD prevents formation much more damaging peroxynitrite ONOO − + NO · → maintains physiologically relevant level nitric oxide (NO ), important molecule neurotransmission, inflammation, vasodilation. second-line pathway exogenous diet-derived small-molecule antioxidants. third-line ensured repair oxidized proteins biomolecules variety enzyme review briefly discusses endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) (e.g., smoking, radiation, drugs, pollution) sources (superoxide radical, peroxide, hydroxyl peroxyl hypochlorous acid, peroxynitrite). Attention has been given system provided SOD, CAT, GPx. chemical molecular mechanisms enzymes, enzyme-related (cancer, cardiovascular, lung, metabolic, GPx4) cellular processes ferroptosis discussed. Potential therapeutic applications mimics recent progress metal-based (copper, iron, cobalt, molybdenum, cerium) nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) also Moreover, attention action low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids β-carotene, lycopene, lutein), flavonoids quercetin, anthocyanins, epicatechin), (GSH)), activation transcription factors Nrf2, protection against diseases. Given that there discrepancy preclinical clinical studies, approaches may result greater pharmacological success therapies subject discussion.

Language: Английский

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Fundamentals of redox regulation in biology

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(9), P. 701 - 719

Published: April 30, 2024

Language: Английский

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Designing nanozymes for in vivo applications

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(10), P. 849 - 868

Published: July 18, 2024

Language: Английский

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Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1314 - 1314

Published: Jan. 21, 2024

Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from substrates oxygen produce adenosine triphosphate. also regulate proliferation, metastasis, and deterioration. The flow in mitochondrial respiratory chain generates reactive species (ROS), which harmful cells at high levels. stress caused by ROS accumulation has been associated with an increased risk cancer, cardiovascular liver diseases. Glutathione (GSH) is abundant cellular antioxidant that primarily synthesized cytoplasm delivered mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within A long-term imbalance ratio mGSH can cause dysfunction, apoptosis, necroptosis, ferroptosis, may lead disease. This study aimed review physiological functions, anabolism, variations organ tissue accumulation, delivery GSH mitochondria relationships between levels, GSH/GSH disulfide (GSSG) ratio, programmed death, ferroptosis. We discuss diseases deficiency related therapeutics.

Language: Английский

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Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(9), P. 1502 - 1518.e9

Published: Aug. 27, 2024

Language: Английский

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Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116432 - 116432

Published: March 22, 2024

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing crucial role the early and sustained phases of DNA damage genomic epigenetic instability, both which are intricately linked to development tumors. The molecular pathways contributing carcinogenesis this context, particularly those related double-strand single-strand breaks DNA, serve as indicators due cancer cases, well factors instability through ectopic expressions. has been considered therapeutic target for many years, an increasing number studies have highlighted promising effectiveness natural products treatment. In regard, we present significant research on targeting oxidative using molecules underscore essential cancer. consequences stress, especially also offer prospects. use epi-drugs capable modulating reorganizing network is beginning emerge remarkably. review, emphasize close connections between tumor transformation, while highlighting substances antioxidants anti-tumoral context.

Language: Английский

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Oxidative Stress and Age-Related Tumors

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1109 - 1109

Published: Sept. 13, 2024

Oxidative stress is the result of imbalance between reactive oxygen and nitrogen species (RONS), which are produced by several endogenous exogenous processes, antioxidant defenses consisting molecules that protect biological systems from free radical toxicity. a major factor in aging process, contributing to accumulation cellular damage over time. biomolecules, leads DNA alterations, lipid peroxidation, protein oxidation, mitochondrial dysfunction resulting senescence, immune system tissue dysfunctions, increased susceptibility age-related pathologies, such as inflammatory disorders, cardiovascular neurodegenerative diseases, diabetes, cancer. stress-driven mutations, or methylation histone modification, alter gene expression, key determinants tumor initiation, angiogenesis, metastasis, therapy resistance. Accumulation genetic epigenetic damage, oxidative contributes, eventually unrestrained cell proliferation, inhibition differentiation, evasion death, providing favorable conditions for tumorigenesis. Colorectal, breast, lung, prostate, skin cancers most frequent aging-associated malignancies, implicated their pathogenesis behavior. Our aim shed light on molecular mechanisms link stress, aging, cancers, highlighting impact both RONS antioxidants, provided diet exercise, immunity, development an antitumor response. The dual role ROS physiological regulators signaling responsible well its use anti-tumor therapeutic purposes, will also be discussed. Managing crucial promoting healthy reducing risk tumors.

Language: Английский

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Oxidative Stress and Cardiovascular Complications in Type 2 Diabetes: From Pathophysiology to Lifestyle Modifications

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 72 - 72

Published: Jan. 9, 2025

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly increases the risk of cardiovascular disease, which leading cause morbidity and mortality among diabetic patients. A central pathophysiological mechanism linking T2DM to complications oxidative stress, defined as an imbalance between reactive oxygen species (ROS) production body’s antioxidant defenses. Hyperglycemia in promotes stress through various pathways, including formation advanced glycation end products, activation protein kinase C, mitochondrial dysfunction, polyol pathway. These processes enhance ROS generation, endothelial vascular inflammation, exacerbation damage. Additionally, disrupts nitric oxide signaling, impairing vasodilation promoting vasoconstriction, contributes complications. This review explores molecular mechanisms by pathogenesis disease T2DM. It also examines potential lifestyle modifications, such dietary changes physical activity, reducing mitigating risks this high-risk population. Understanding these critical for developing targeted therapeutic strategies improve outcomes

Language: Английский

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Role of Antioxidants in Skin Aging and the Molecular Mechanism of ROS: A Comprehensive Review

Aspects of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100063 - 100063

Published: Jan. 1, 2025

Language: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

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