Pharmacological Actions of Melatonin in Oxygen Radical Pathophysiology

Russel Reiter, Lei Tang, Joaquin J. Garcia, and Antonio Munoz-Hoyos

Life Science, 1997; Vol 60, No 25

Melatonin, the chief secretory product of the pineal gland, was recently found to be a free radical scavenger and antioxidant. The review briefly summarizes the published reports supporting this conclusion. Melatonin is believed to work via electron donation to directly detoxify free radicals such as the highly toxic hydroxyl radical. Additionally, both in vitro and in vivo experiments, melatonin has been found to protect cells, tissues and organs against oxidative damage induced by a variety of free radical generating agents and processes, e.g., the carcinogen safrole, lipopolysaccharide, kainic acid, Fenton reagents, potassium cyanide, L-cysteine , excessive exercise, glutathione depletion, carbon tetrachloride, ischemia-reperfusion, MTPP, amyloid β (25-35 amino acid residue) protein, and ionizing radiation. As an antioxidant, Melatonin  is effective in protecting nuclear DNA, membrane lipids and possibly cystolic proteins from oxidative damage. Also, melatonin has been reported to alter the activities of enzymes which improve the total antioxidative defense capacity of the organism, i.e. siperoxide dimustase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate deydorgenase and nitric oxide synthase. Most studies have used pharmacological concentrations or doses of melatonin to protect against free radical damage; in a few studies physiological levels of the indole have been shown to be beneficial against oxidative stress. Melatonin's function as a free radical scavenger and antioxidant is likely supported by the ease with which it crosses morphophysiological barriers, e.g. the blood-brain barrier, and enters cells and subcellular compartments. Whether the quantity of melatonin produced in vertebrate species sufficient to significantly the influence the total antioxidative defense capacity of the organism remain unknown, but its pharmacological benefits seem assured considering the low toxicity of the molecule.

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