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: 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 and endoplasmic reticulum stress: relation to autophagy and apoptosis

Journal of Pineal Research, Год журнала: 2015, Номер 59(3), С. 292 - 307

Опубликована: Июль 22, 2015

Endoplasmic reticulum (ER) is a dynamic organelle that participates in number of cellular functions by controlling lipid metabolism, calcium stores, and proteostasis. Under stressful situations, the ER environment compromised, protein maturation impaired; this causes misfolded proteins to accumulate characteristic stress response named unfolded (UPR). UPR protects cells from contributes homeostasis re-establishment; however, during prolonged stress, activation promotes cell death. stressors can modulate autophagy which turn, depending situation, induces survival or Interactions different autophagy- apoptosis-related also common signaling pathways have been found, suggesting an interplay between these processes, although their features are still unknown. A pathologies including metabolic, neurodegenerative cardiovascular diseases, cancer, inflammation, viral infections associated with leading growing interest targeting components as therapeutic strategy. Melatonin has variety antioxidant, anti-inflammatory, antitumor effects. As such, it modulates apoptosis cancer cells, neurodegeneration development liver diseases well other pathologies. Here, we review effects melatonin on main mechanisms, focusing its ability regulate autophagic apoptotic processes. studies analyzed modulation indole remains limited, further research necessary for better understanding crosstalk autophagy, clearly delineate mechanisms responses.

Язык: Английский

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Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

International Journal of Molecular Sciences, Год журнала: 2017, Номер 18(4), С. 843 - 843

Опубликована: Апрель 17, 2017

There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, molecular mechanisms underpinning these inhibitory actions have been proposed. What rather perplexing, however, large number of processes by which reportedly restrains development growth. These diverse suggest what being observed are merely epiphenomena an underlying more fundamental action remains to be disclosed. Some arresting on clearly membrane receptor-mediated while others receptor-independent involve direct intracellular this ubiquitously-distributed molecule. While emphasis melatonin/cancer research has role indoleamine in restraining breast cancer, changing quickly with types having shown susceptible inhibition melatonin. several facets could immediate applications clinical level. Many studies melatonin's co-administration improves sensitivity cancers conventional drugs. Even important findings renders previously totally resistant treatment sensitive same therapies. Melatonin also inhibits associated limiting entrance cells into vascular system preventing them from establishing secondary growths distant sites. This particular importance since often significantly contributes death patient. Another area deserves additional consideration related capacity reducing toxic consequences anti-cancer drugs increasing their efficacy. Although information available for than a decade, it not adequately exploited if only beneficial patients its ability attenuate acute long-term drug toxicity, should used improve physical wellbeing patients. The experimental findings, advantages using as co-treatment therapies would far exceed improvements

Язык: Английский

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Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release

Proceedings of the National Academy of Sciences, Год журнала: 2017, Номер 114(38)

Опубликована: Сен. 5, 2017

G protein-coupled receptors (GPCRs) are classically characterized as cell-surface transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised the melatonin type 1 receptor (MT

Язык: Английский

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Melatonin reprogramming of gut microbiota improves lipid dysmetabolism in high‐fat diet‐fed mice

Journal of Pineal Research, Год журнала: 2018, Номер 65(4)

Опубликована: Сен. 19, 2018

Melatonin has been shown to improve lipid metabolism and gut microbiota communities in animals humans; however, it remains know whether melatonin prevents obesity through microbiota. Here, we found that high-fat diet promoted the accumulation intestinal dysbiosis mice, while oral supplementation alleviated reversed dysbiosis, including diversity of microbiota, relative abundances Bacteroides Alistipes, functional profiling microbial communities, such as energy metabolism, carbohydrate metabolism. Interestingly, failed alleviate high-fat-induced antibiotic-treated mice; transplantation from melatonin-treated mice diet-induced metabolic disorders. Notably, short-chain fatty acids were decreased diet-fed treatment improved production acetic acid. Correlation analysis a marked correlation between acid Alistipes. Importantly, sodium acetate also Taken together, our results suggest improves potential mechanisms may be associated with reprogramming especially, Alistipes-mediated production. Future studies are needed for patients syndrome fully understand melatonin's effects on body weight profiles mechanism

Язык: Английский

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Exogenous Melatonin Confers Salt Stress Tolerance to Watermelon by Improving Photosynthesis and Redox Homeostasis

Frontiers in Plant Science, Год журнала: 2017, Номер 8

Опубликована: Март 1, 2017

Melatonin, a pleiotropic signal molecule, has been shown to play important roles in the regulation of plant growth, development, and responses environmental stresses. Since few species have investigated unveil effect exogenous melatonin on salt stress, underlying mechanism melatonin-mediated stress tolerance other still remains largely unknown. In this study, effects leaf photosynthesis redox homeostasis watermelon were examined under (300 mM NaCl) along with different doses (50, 150, 500 μM) pretreatment. NaCl inhibited increased accumulation reactive oxygen membrane damage leaves seedlings. However, pretreatment roots alleviated NaCl-induced decrease photosynthetic rate oxidative dose-dependent manner. The protection by was closely associated inhibition stomatal closure improved light energy absorption electron transport photosystem II, while reduction attributed coupled enhanced activities antioxidant enzymes. This study unraveled crucial role mitigation thus can be implicated management salinity cultivation.

Язык: Английский

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SIRT3-SOD2-mROS-dependent autophagy in cadmium-induced hepatotoxicity and salvage by melatonin

Autophagy, Год журнала: 2015, Номер 11(7), С. 1037 - 1051

Опубликована: Июнь 29, 2015

Cadmium is one of the most toxic metal compounds found in environment. It well established that Cd induces hepatotoxicity humans and multiple animal models. Melatonin, a major secretory product pineal gland, has been reported to protect against Cd-induced hepatotoxicity. However, mechanism behind this protection remains be elucidated. We exposed HepG2 cells different concentrations cadmium chloride (2.5, 5, 10 μM) for 12 h. induced mitochondrial-derived superoxide anion-dependent autophagic cell death. Specifically, decreased SIRT3 protein expression activity promoted acetylation SOD2, dismutase 2, mitochondrial, thus decreasing its activity, key enzyme involved mitochondrial ROS production, although did not disrupt interaction between SOD2. These effects were ameliorated by overexpression SIRT3. catalytic mutant (SIRT3(H248Y)) lacking deacetylase lost capacity suppress autophagy. Notably, melatonin treatment enhanced but SIRT3, inhibited O2(•-) production suppressed autophagy μM Cd. Moreover, 3-(1H-1,2,3-triazol-4-yl)pyridine, confirmed selective inhibitor, blocked melatonin-mediated suppression inhibiting SIRT3-SOD2 signaling. Importantly, death enhancing vivo. results suggest exerts hepatoprotective effect on O2(•-)-stimulated dependent SIRT3/SOD2 pathway.

Язык: Английский

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Phytomelatonin: Assisting Plants to Survive and Thrive

Molecules, Год журнала: 2015, Номер 20(4), С. 7396 - 7437

Опубликована: Апрель 22, 2015

This review summarizes the advances that have been made in terms of identified functions melatonin plants. Melatonin is an endogenously-produced molecule all plant species investigated. Its concentration organs varies different tissues, e.g., roots versus leaves, and with their developmental stage. As animals, pathway synthesis plants utilizes tryptophan as essential precursor molecule. inducible when they are exposed to abiotic stresses (extremes temperature, toxins, increased soil salinity, drought, etc.) well biotic (fungal infection). aids root growth, leaf morphology, chlorophyll preservation fruit development. There also evidence exogenously-applied improves seed germination, growth crop yield its application products post-harvest shows ripening may improve food quality. Since was only discovered two decades ago, there still a great deal learn about functional significance It hope authors current will serve stimulus for scientists join endeavor clarifying function this phylogenetically-ancient particularly reference mechanisms by which mediates multiple actions.

Язык: Английский

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Melatonin and its metabolites vs oxidative stress: From individual actions to collective protection

Journal of Pineal Research, Год журнала: 2018, Номер 65(1)

Опубликована: Июнь 11, 2018

Abstract Oxidative stress (OS) represents a threat to the chemical integrity of biomolecules including lipids, proteins, and DNA. The associated molecular damage frequently results in serious health issues, which justifies our concern about this phenomenon. In addition enzymatic defense mechanisms, there are compounds (usually referred as antioxidants) that offer protection against oxidative events. Among them, melatonin its metabolites constitute particularly efficient family. They OS individual entities through wide variety mechanisms electron transfer, hydrogen radical adduct formation, metal chelation, by repairing biological targets. fact, many them can be classified multipurpose antioxidants. However, what seems unique melatonin's family is their collective effects. Because members metabolically related, most expected present living organisms wherever produced. Therefore, exerted may viewed result combined antioxidant effects parent molecule metabolites. Melatonin's rather exceptional regard, offering versatile OS. It certainly one best nature's defenses damage.

Язык: Английский

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