Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials

Abstract

Oxidative stress plays a key role in the pathogenesis of aging and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nutritional, environmental, and chemical factors can induce the overproduction of the superoxide anion radical in both the cytosol and mitochondria. This is the first and key event that leads to the activation of pathways involved in the development of several metabolic diseases that are related to oxidative stress. As oxidation of essential molecules continues, it turns to nitrooxidative stress because of the involvement of nitric oxide in pathogenic processes. Once peroxynitrite forms, it damages via two distinctive mechanisms. First, it has direct toxic effects leading to lipid peroxidation, protein oxidation, and DNA damage. This mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Classic antioxidants, including vitamins A, C, and E, have often failed to exhibit beneficial effects in metabolic diseases and aging. Melatonin is a multifunctional indolamine that counteracts virtually all pathophysiologic steps and displays significant beneficial actions against peroxynitrite-induced cellular toxicity. This protection is related to melatonin′s antioxidative and antiinflammatory properties. Melatonin has the capability of scavenging both oxygen-and nitrogenbased reactants, including those formed from peroxynitrite, and blocking transcriptional factors, which induce proinflammatory cytokines. Accumulating evidence suggests that this nontoxic indolamine may be useful either as a sole treatment or in conjunction with other treatments for inhibiting the biohazardous actions of nitrooxidative stress.

Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury

“…Melatonin exerts its anti-oxidative actions by increasing the activity of superoxide dismutase and glutathione peroxidase after I/R, thereby decreasing MDA accumulation in postischemic hepatic tissue [23,26]. Thus, melatonin within the MDDP protocol may have contributed to the prevention of reperfusion injury by abrogating the oxygen radical actions and thus the MDA accumulation.…”

“…Melatonin and its metabolites are potent anti-oxidants that are well tolerated and non-toxic [23]. Melatonin has been reported to reduce hepatocellular damage after warm I/R [24] and to improve liver function after cold storage and reperfusion [24][25][26].…”

Melatonin Ameliorates Burn-Induced Liver Injury by Modulation of Nrf2 and Nf- kB Signaling Pathways

“…This hormone is known to regulate the circadian rhythms induced by a short light dark cycle and the circadian rhythms [14,15]. A number of studies demonstrate that melatonin is an interesting pharmacological agent in the treatment of inflammatory conditions [8][9][10][11][12][13][14][15][16]. The beneficial effect of melatonin in these studies is associated with: 1) antioxidant effect of this indole and 2) modulation of the inflammatory response.…”

“…It passes freely through membranes and distributes in all subcellular compartments [5]. These evidences suggest that these pleiotropic functions of melatonin may be used clinically under conditions where its circulating levels are reduced [9,10]. Because of its antioxidant, anti-inflammatory and anti-apoptotic effects, exogenous melatonin attenuates ischemia/reperfusion and hepatotoxins induced liver injury [11][12][13].…”

The role of melatonin in development of gestational diabetes mellitus

“…Прежде всего, мелатонин и его метаболиты функционируют как прямые поглотители образующихся при беременности свободных радикалов, стимули-руют антиоксидантные ферменты, обеспечивая тем самым устойчивую защиту от свободнора-дикального повреждения на клеточном и тка-невом уровнях в единой системе мать -плацен-та -плод [64][65][66].…”