Melatonin: a novel protective agent against oxidative injury of the ischemic/reperfused heart

This brief review summarizes the recently obtained evidence which illustrates the beneficial effects of the endogenously produced antioxidant, melatonin, in reducing tissue damage and reversing cardiac pathophysiology in models of experimental ischemia/reperfusion. The report also describes the actions of other antioxidants, especially vitamin E and antioxidative enzymes, in altering the degree of ischemia/reperfusion damage in the heart. Based on the data available, melatonin seems to have advantages over other antioxidants tested in terms of ameliorating the hypoxia and reoxygenation-induced damage. While the bulk of the studies that have used melatonin to overcome cardiac injury following transient arterial occlusion and subsequent reperfusion have used pharmacological doses to achieve protection, two recent reports have further shown that merely reducing endogenous circulating concentrations of melatonin (by surgical removal of a source of melatonin, i.e. the pineal gland) exaggerates the degree of injury and reduces survival of animals as a result of induced ischemia/reperfusion of the heart. These findings are consistent with observations in other organs where the loss of physiological concentrations of melatonin results in increased oxidative damage during hypoxia and reoxygenation. These findings have implications for the elderly since in the aged endogenous levels of melatonin are naturally reduced thereby possibly predisposing them to more severe cardiac damage during a heart attack. To date, the bulk of the studies relating to the protective actions of melatonin in reducing cardiac ischemia/reperfusion injury have used the rat as the experimental model. Considering the high efficacy of melatonin in limiting ischemia/reperfusion damage as well as melatonin's low toxicity, the studies should be expanded to include other species and models of cardiac ischemia/reperfusion. The results of these investigations would help to clarify the potential importance of the use of melatonin in situations of oxidative damage to the heart in humans. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.