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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Extrapineal melatonin: sources, regulation, and potential functions

Cellular and Molecular Life Sciences, Journal Year: 2014, Volume and Issue: 71(16), P. 2997 - 3025

Published: Feb. 19, 2014

Language: Английский

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Melatonin: an ancient molecule that makes oxygen metabolically tolerable

Journal of Pineal Research, Journal Year: 2015, Volume and Issue: 59(4), P. 403 - 419

Published: Aug. 14, 2015

Abstract Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti‐inflammatory immunoregulating molecule, an oncostatic agent. We hypothesize that the initial primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5–3.2 billion years ago, was antioxidant. The evolution antioxidant by this organism necessary photosynthesis associated generation toxic‐free radicals. other secondary functions came about much later evolution. also surmise mitochondria chloroplasts may be sites synthesis all eukaryotic cells possess these organelles. This prediction made basis eukaryotes developed from purple nonsulfur bacteria (which produce melatonin) cyanobacteria when they were engulfed early eukaryotes. Thus, we speculate melatonin‐synthesizing retained organelles became chloroplasts, respectively. That are likely formation supported observation organelle contains high levels not impacted blood concentrations. has remarkable array means it thwarts oxidative damage. It, well its metabolites, differentially effective scavenging variety reactive oxygen nitrogen species. Moreover, metabolites modulate large number antioxidative pro‐oxidative enzymes, leading to reduction metabolizing/producing enzymes mediated Keap1‐Nrf2‐ ARE pathway. Beyond direct indirect effects, physiological metabolic advantages enhance ability limit stress.

Language: Английский

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Melatonin: a well‐documented antioxidant with conditional pro‐oxidant actions

Journal of Pineal Research, Journal Year: 2014, Volume and Issue: 57(2), P. 131 - 146

Published: July 25, 2014

Abstract Melatonin ( N ‐acetyl‐5‐methoxytryptamine), an indoleamine produced in many organs including the pineal gland, was initially characterized as a hormone primarily involved circadian regulation of physiological and neuroendocrine function. Subsequent studies found that melatonin its metabolic derivatives possess strong free radical scavenging properties. These metabolites are potent antioxidants against both ROS (reactive oxygen species) RNS nitrogen species). The mechanisms by which protect radicals oxidative stress include direct products, induction expression antioxidant enzymes, reduction activation pro‐oxidant maintenance mitochondrial homeostasis. In vitro vivo studies, has been shown to reduce damage lipids, proteins DNA under very wide set conditions where toxic known be produced. Although vast majority proved capacity derivatives, few using cultured cells promoted generation at pharmacological concentrations μ m range) several tumor nontumor cells; thus, functioned conditional pro‐oxidant. Mechanistically, may stimulate production through interaction with calmodulin. Also, interact complex III or transition pore promote production. Whether functions is not well documented; whether reported actions come into play live organisms remains established.

Language: Английский

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Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

Molecules, Journal Year: 2015, Volume and Issue: 20(10), P. 18886 - 18906

Published: Oct. 16, 2015

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It present in almost all or organisms. Its synthetic pathway depends on the species which it measured. For example, tryptophan to melatonin differs plants and animals. speculated that machinery eukaryotes was inherited from bacteria as result of endosymbiosis. However, melatonin's mechanisms microorganisms are currently unknown. metabolism highly complex these enzymatic processes having evolved cytochrome C. In addition its degradation, metabolized via pseudoenzymatic free radical interactive processes. The metabolic products overlap often difficult determine process dominant. under oxidative stress, may be featured over others. Because complexity degradative processes, expected additional novel metabolites will identified future investigations. original primary function early life forms such unicellular organisms scavenger antioxidant. During evolution, selected signaling transduce environmental photoperiodic information into an endocrine message multicellular for other purposes well. As antioxidant, exhibits several unique features differ classic antioxidants. These include cascade reaction radicals capacity induced moderate stress. make potent endogenously-occurring antioxidant protects catastrophic

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 promotes water‐stress tolerance, lateral root formation, and seed germination in cucumber (Cucumis sativus L.)

Journal of Pineal Research, Journal Year: 2012, Volume and Issue: 54(1), P. 15 - 23

Published: May 31, 2012

A comprehensive investigation was carried out to determine the changes that occurred in water-stressed cucumber (Cucumis sativus L.) response melatonin treatment. We examined potential roles of during seed germination and root generation measured its effect on reactive oxygen species (ROS) levels, antioxidant enzyme activities, photosynthesis. Melatonin alleviated polyethylene glycol induced inhibition germination, with 100 μm melatonin-treated seeds showing greatest rate. stimulated vitality increased root:shoot ratio; therefore, may have an strengthening roots. treatment significantly reduced chlorophyll degradation. Seedlings treated clearly showed a higher photosynthetic rate, thus reversing water stress. Furthermore, ultrastructure chloroplasts leaves maintained after The levels activities ROS scavenging enzymes, i.e., superoxide dismutase, peroxidase, catalase, were also by melatonin. These results suggest adverse effects stress can be minimized application

Language: Английский

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Melatonin: Exceeding Expectations

Physiology, Journal Year: 2014, Volume and Issue: 29(5), P. 325 - 333

Published: Sept. 1, 2014

Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm regulation, sleep, cancer inhibition. The actions relate to melatonin's ability function in the detoxification of free radicals, thereby protecting critical molecules from destructive effects oxidative stress under conditions ischemia/reperfusion injury (stroke, heart attack), ionizing radiation, drug toxicity, among others. has applications physiology medicine.

Language: Английский

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Melatonin as a Hormone: New Physiological and Clinical Insights

Endocrine Reviews, Journal Year: 2018, Volume and Issue: 39(6), P. 990 - 1028

Published: Sept. 12, 2018

Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides produced peripheral tissues and acting as an autocrine paracrine signal, melatonin centrally synthetized by neuroendocrine organ, the pineal gland. Independently of considered species, hormone always during night its production secretory episode duration are directly dependent on length night. As tightly linked light/dark cycle, main hormonal systemic integrative action coordinate behavioral physiological adaptations environmental geophysical day season. The circadian signal daily regularity, contrast between concentrations, specially developed ways action. During episode, coordinates adaptive physiology through immediate effects primes responses prospective that will only appear at daytime, when absent. Similarly, annual history central nervous/endocrine system seasons come. Remarkably, maternal programs fetuses' behavior cope with cycle season after birth. These unique turn into biological time-domain–acting molecule. review focuses above considerations, proposes putative classification clinical dysfunctions, discusses general guidelines therapeutic use melatonin.

Language: Английский

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Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin's primary function and evolution in eukaryotes

Journal of Pineal Research, Journal Year: 2012, Volume and Issue: 54(2), P. 127 - 138

Published: Oct. 12, 2012

Abstract Mitochondria and chloroplasts are major sources of free radical generation in living organisms. Because this, these organelles require strong protection from radicals associated oxidative stress. Melatonin is a potent scavenger antioxidant. It meets the criteria as mitochondrial chloroplast Evidence has emerged to show that both mitochondria may have capacity synthesize metabolize melatonin. The activity arylalkylamine N ‐acetyltransferase ( AANAT ), reported rate‐limiting enzyme melatonin synthesis, been identified mitochondria, high levels also found this organelle. From an evolutionary point view, precursor probably purple nonsulfur bacterium, particularly, R hodospirillum rubrum, descendents cyanobacteria. These bacterial species were endosymbionts host proto‐eukaryotes gradually transformed into cellular organelles, is, chloroplasts, respectively, thereby giving rise eukaryotic cells. Of special importance, bacteria . rubrum ) cyanobacteria activities required for synthesis detected primitive species. our hypothesis original sites early stage endosymbiotic organisms; synthetic was carried eukaryotes by above‐mentioned bacteria. Moreover, their biosynthetic capacities preserved during evolution. In most, if not all cells, continue be primary generation. production other compartments derived chloroplasts. On basis hypothesis, it possible explain why plants typically higher than do animals. plants, likely melatonin, while animal cells contain only mitochondria. produced used protect important against stress preserve physiological functions. superior beneficial effects frequently reported.

Language: Английский

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