Many Roles Of Melatonin: Diversity And Complexity Of Reaction Pathways

Melatonin (N-acetyl-5-methoxy tryptamine) is well known as a free radical scavenger and antioxidant involved in different biological and physiological regulation such as modulation of circadian rhythms, seasonal reproduction, retinal physiology and sleep regulation. Synthetic melatonin is available commercially, and its supplements have been used clinically to treat a variety of medical conditions such as jet lag, shift work and sleep disorders. Recent studies demonstrated that melatonin serves as an inhibitor of myeloperoxidase (MPO) under physiological-like conditions. Melatonin-dependent inhibition of MPO occurred with a wide range of concentrations that span various physiological and supplemental ranges. Myeloperoxidase is enzyme involved in leukocyte-mediated host defenses but plays a pathogenic role during chronic inflammatory conditions. MPO levels implicate inflammation in the walls of coronary arteries, which in turn, may indicate a risk for heart disease or heart attack. Thus, supplementary concentrations of melatonin can influence physiological and pathophysiological role of MPO. In addition, MPO modulates nitric oxide production, so melatonin can indirectly affects nitric oxide concentration. Amounting evidence shows new emerging role of melatonin and its metabolites beyond the classic one. This review focuses on newly discovered mechanistic pathways of melatonin activity that has to be taken into consideration when discussing pharmacological uses of melatonin.