Melatonin as an antioxidant: under promises but over delivers

Journal of Pineal Research, Journal Year: 2016, Volume and Issue: 61(3), P. 253 - 278

Published: Aug. 8, 2016

Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via variety means: direct detoxification reactive oxygen and nitrogen species indirectly by stimulating antioxidant enzymes while suppressing the activity pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved Fenton/Haber-Weiss reactions; doing so, reduces formation devastatingly toxic hydroxyl radical resulting reduction stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations mitochondria, likely aid capacity resist cellular apoptosis. There credible evidence suggest that should be classified as mitochondria-targeted antioxidant. prevent damage associated physiological debilitation well documented numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially brain (stroke) heart (heart attack). Melatonin, antiradical mechanisms, toxicity noxious prescription drugs methamphetamine, drug abuse. Experimental findings indicate renders treatment-resistant cancers sensitive various therapeutic agents may useful, due multiple delaying perhaps treating age-related diseases dehumanizing conditions. has been effectively used combat stress, inflammation apoptosis restore tissue function human trials; efficacy supports more extensive use wider studies. The high-safety profile bolsters conclusion. current feeling authors that, view widely diverse beneficial functions have reported for melatonin, merely epiphenomena fundamental, yet-to-be identified basic action(s) ancient molecule.

Language: Английский

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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 Synthesis and Function: Evolutionary History in Animals and Plants

Frontiers in Endocrinology, Journal Year: 2019, Volume and Issue: 10

Published: April 17, 2019

Melatonin is an ancient molecule that can be traced back to the origin of life. Melatonin's initial function was likely as a free radical scavenger. presumably evolved in bacteria; it has been measured both α-proteobacteria and photosynthetic cyanobacteria. In early evolution, bacteria were phagocytosed by primitive eukaryotes for their nutrient value. According endosymbiotic theory, ingested eventually developed symbiotic association with host eukaryotes. The into mitochondria while cyanobacteria became chloroplasts organelles retained ability produce melatonin. Since these have persisted present day, all species ever existed or currently exist may continue synthesize melatonin (animals plants) (plants) where functions antioxidant. other functions, including its multiple receptors, later evolution. day animals, via receptor-mediated means, regulation sleep, modulation circadian rhythms, enhancement immunity, multifunctional oncostatic agent, etc., retaining reduce oxidative stress processes are, part, receptor-independent. plants, continues reducing well promoting seed germination growth, improving resistance, stimulating immune system modulating rhythms; single receptor identified land plants controls stomatal closure on leaves. synthetic pathway varies somewhat between animals. amino acid, tryptophan, necessary precursor taxa. tryptophan initially hydroxylated 5-hydroxytryptophan which then decarboxylated formation serotonin. Serotonin either acetylated

Language: Английский

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Melatonin and its relationship to plant hormones

Annals of Botany, Journal Year: 2017, Volume and Issue: 121(2), P. 195 - 207

Published: Aug. 17, 2017

Plant melatonin appears to be a multi-regulatory molecule, similar those observed in animals, with many specific functions plant physiology. In recent years, the number of studies on plants has increased significantly. One most studied actions is its effect biotic and abiotic stress, such as that produced by drought, extreme temperatures, salinity, chemical pollution UV radiation, among others.

Language: Английский

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Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas

Cellular and Molecular Life Sciences, Journal Year: 2017, Volume and Issue: 74(21), P. 3863 - 3881

Published: Sept. 1, 2017

Language: Английский

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Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts

Journal of Pineal Research, Journal Year: 2016, Volume and Issue: 61(4), P. 426 - 437

Published: Sept. 7, 2016

Melatonin is an animal hormone as well a signaling molecule in plants. It was first identified plants 1995, and almost all enzymes responsible for melatonin biosynthesis had already been characterized these species. from tryptophan requires four-step reactions. However, six genes, that is, TDC, TPH, T5H, SNAT, ASMT, COMT, have implicated the synthesis of plants, suggesting presence multiple pathways. Two major pathways proposed based on enzyme kinetics: One tryptophan/tryptamine/serotonin/N-acetylserotonin/melatonin pathway, which may occur under normal growth conditions; other tryptophan/tryptamine/serotonin/5-methoxytryptamine/melatonin when produce large amounts serotonin, example, upon senescence. The biosynthetic capacity associated with conversion to serotonin much higher than melatonin, yields low level Many intermediates are produced various subcellular compartments, such cytoplasm, endoplasmic reticulum, chloroplasts, either facilitates or impedes subsequent enzymatic steps. Depending pathways, final sites vary at cytoplasm differentially affect mode action

Language: Английский

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Update on melatonin receptors: IUPHAR Review 20

British Journal of Pharmacology, Journal Year: 2016, Volume and Issue: 173(18), P. 2702 - 2725

Published: June 17, 2016

Melatonin receptors are seven transmembrane‐spanning proteins belonging to the GPCR superfamily. In mammals, two melatonin receptor subtypes exist ‐ MT 1 and 2 encoded by MTNR1A MTNR1B genes respectively. The current review provides an update on corresponding subcommittee of International Union Basic Clinical Pharmacology. We will highlight recent developments ligands, including radioligands, give latest phenotyping results knockout mice. status perspectives structure be summarized. physiological importance dimers biologically important type diabetes‐associated genetic variants discussed. role in physiology disease further exemplified their functions immune system CNS. Finally, antioxidant free radical scavenger properties its relation critically addressed.

Language: Английский

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Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut

Cell, Journal Year: 2020, Volume and Issue: 181(6), P. 1307 - 1328.e15

Published: June 1, 2020

Language: Английский

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The Critical Role of Zinc in Plants Facing the Drought Stress

Agriculture, Journal Year: 2020, Volume and Issue: 10(9), P. 396 - 396

Published: Sept. 7, 2020

Drought stress affects plant growth and development by altering physiological biochemical processes resulting in reduced crop productivity. Zinc (Zn) is an essential micronutrient that plays fundamental roles resistance against the drought regulating various molecular mechanisms. Under stress, Zn application improves seed germination, water relations, cell membrane stability, osmolyte accumulation, stomatal regulation, use efficiency photosynthesis, thus significantly better performance. Moreover, interacts with hormones, increases expression of proteins stimulates antioxidant enzymes for counteracting effects. To appraise potential benefits arising from optimum nutrition, present review we discuss role plants under stress. Our aim to provide a complete, updated picture order orientate future research directions on this topic.

Language: Английский

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Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

International Journal of Molecular Sciences, Journal Year: 2016, Volume and Issue: 17(12), P. 2124 - 2124

Published: Dec. 16, 2016

Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) localized in mitochondria of oocytes and isolated generate melatonin. We have also melatonin a mitochondria-targeted antioxidant. It accumulates with high concentration against gradient. probably achieved an active transportation via mitochondrial transporter(s). protects scavenging reactive oxygen species (ROS), inhibiting permeability transition pore (MPTP), activating uncoupling proteins (UCPs). Thus, maintains optimal membrane potential preserves functions. In addition, biogenesis dynamics regulated most cases, reduces fission elevates their fusion. Mitochondrial exhibit oscillatory pattern which matches circadian secretory rhythm pinealeocytes other cells. Recently, found promote mitophagy improve homeostasis

Language: Английский

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