Melatonin as an antioxidant: under promises but over delivers

Abstract

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

Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition

“…The heart is rich in mitochondria to maintain normal contractile function due to the high energy demands of this organ as well as other tissues 6, 7, 8. Cardiac mitochondria play a critical role and act as a power plant for cardiomyocytes through oxidative phosphorylation 9, 10, 11.…”

The melatonin immunomodulatory actions in radiotherapy

“…Melatonin has two important metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK). Of these, AFMK is the most abundant (Manchester et al 2015;Reiter et al 2016).…”

Melatonin as an Agent for Cardioprotection in Patients with ST-Elevation Myocardial Infarction and Short Ischaemic Time

“…Moreover, decreased melatonin levels were reported in various pathological conditions including hypertension with nondipper pattern, congestive heart failure, ischemic heart disease, and in patients after acute myocardial infarction [4,5]. We point out that there have been several recent systematic reviews on this topic that the reader might find useful [4,[6][7][8].…”

“…Moreover, decreased melatonin levels were reported in various pathological conditions including hypertension with nondipper pattern, congestive heart failure, ischemic heart disease, and in patients after acute myocardial infarction [4,5]. We point out that there have been several recent systematic reviews on this topic that the reader might find useful [4,[6][7][8].Recently, our group published the methodology and results of MARIA (Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty trial), a randomized, double-blind, placebo controlled trial [9]. Briefly, patients were recruited in three Spanish centers.…”