Melatonin as an antioxidant: under promises but over delivers

Journal of Pineal Research, Год журнала: 2016, Номер 61(3), С. 253 - 278

Опубликована: Авг. 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.

Язык: Английский

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Melatonin as a natural ally against oxidative stress: a physicochemical examination

Journal of Pineal Research, Год журнала: 2011, Номер 51(1), С. 1 - 16

Опубликована: Июнь 14, 2011

Abstract: Oxidative stress has been proven to be related the onset of a large number health disorders. This chemical is triggered by an excess free radicals, which are generated in cells because wide variety exogenous and endogenous processes. Therefore, finding strategies for efficiently detoxifying radicals become subject great interest, from both academic practical points view. Melatonin ubiquitous versatile molecule that exhibits most desirable characteristics good antioxidant. The amount data gathered so far regarding protective action melatonin against oxidative overwhelming. However, rather little known concerning mechanisms involved this activity. review summarizes current progress understanding physicochemical insights radical–scavenging activity melatonin. Thus far, there general agreement electron transfer hydrogen main reactions with radicals. relative importance other also analyzed. nature reacting radical influence on different these reactions. point discussed detail review. Based available data, it concluded protects mechanisms. Moreover, proposed even though referred as expression darkness, perhaps could light health.

Язык: Английский

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Extrapineal melatonin: sources, regulation, and potential functions

Cellular and Molecular Life Sciences, Год журнала: 2014, Номер 71(16), С. 2997 - 3025

Опубликована: Фев. 19, 2014

Язык: Английский

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Melatonin: an ancient molecule that makes oxygen metabolically tolerable

Journal of Pineal Research, Год журнала: 2015, Номер 59(4), С. 403 - 419

Опубликована: Авг. 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.

Язык: Английский

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Melatonin—A pleiotropic, orchestrating regulator molecule

Progress in Neurobiology, Год журнала: 2010, Номер 93(3), С. 350 - 384

Опубликована: Дек. 29, 2010

Язык: Английский

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

Molecules, Год журнала: 2015, Номер 20(10), С. 18886 - 18906

Опубликована: Окт. 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

Язык: Английский

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Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science

Journal of Experimental Botany, Год журнала: 2011, Номер 63(2), С. 577 - 597

Опубликована: Окт. 20, 2011

The presence of melatonin in plants is universal. Evidence has confirmed that a major portion the synthesized by themselves even though homologue classic arylalkylamine N-acetyltransferase (AANAT) not been identified as yet plants. Thus, serotonin N-acetylating enzyme may differ greatly from animal AANAT with regard to sequence and structure. This would imply multiple evolutionary origins enzymes these catalytic properties. A primary function serve first line defence against internal environmental oxidative stressors. much higher levels compared those found animals are thought be compensatory response which lack means mobility, unlike animals, coping harsh environments. Importantly, remarkably high concentrations have measured popular beverages (coffee, tea, wine, beer) crops (corn, rice, wheat, barley, oats). Billions people worldwide consume products daily. beneficial effects on human health derived consumption must considered. also indicates an ability increase production crops. mechanisms involve roles preservation chlorophyll, promotion photosynthesis, stimulation root development. Transgenic enhanced content could probably lead breakthroughs crop agriculture improve general humans.

Язык: Английский

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Melatonin Synthesis and Function: Evolutionary History in Animals and Plants

Frontiers in Endocrinology, Год журнала: 2019, Номер 10

Опубликована: Апрель 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

Язык: Английский

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Melatonin as a Hormone: New Physiological and Clinical Insights

Endocrine Reviews, Год журнала: 2018, Номер 39(6), С. 990 - 1028

Опубликована: Сен. 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.

Язык: 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, Год журнала: 2012, Номер 54(2), С. 127 - 138

Опубликована: Окт. 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.

Язык: Английский

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