Prevention of ischemia/reperfusion-induced cardiac apoptosis and injury by melatonin is independent of glutathione peroxdiase 1.

Abstract

Free-radical generation is one of the primary causes of myocardial ischemia/reperfusion (I/R) injury. Melatonin is an efficient free-radical scavenger and induces the expression of antioxidant enzymes. We have previously shown that melatonin can prevent free-radical-induced myocardial injury. To date, the mechanism underlying melatonin's cardioprotective effect is not clear. In this study, we assessed the ability of melatonin to protect against I/R injury in mice deficient in glutathione peroxidase 1 (Gpx1). Mice hearts were subjected to 40 min of global ischemia in vitro followed by 45 min of reperfusion. Myocardial I/R injury (expressed as % of recovery of left ventricular developed pressure x heart rate) was exacerbated in mice deficient in Gpx1 (51 +/- 3% for Gpx1+/+ mice versus 31 +/- 6% for Gpx1(-/-) mice, P < 0.05). Administration of melatonin for 30 min protected against I/R injury in both Gpx1+/+ mice (72 +/- 4.8%) and Gpx1(-/-) mice (63 +/- 4.7%). This protection was accompanied by a significant improvement in left ventricular end-diastolic pressure and a twofold decrease in lactate dehydrogenase (LDH) level released from melatonin-treated hearts. In another set of experiments, mice were subjected to 50 min of ligation of the left descending anterior coronary artery in vivo followed by 4 hr of reperfusion. The infarct sizes, expressed as the percentage of the area at risk, were significantly larger in Gpx1(-/-) mice than in Gpx1+/+ mice (75 +/- 9% versus 54 +/- 6%, P < 0.05) and were reduced significantly in melatonin-treated mice (31 +/- 3.7% Gpx1(-/-) mice and 33 +/- 6.0% Gpx1+/+ mice). In hearts subjected to 30 min of coronary artery occlusion followed by 3 hr of reperfusion, melatonin-treated hearts had significantly fewer in situ oligo ligation-positive myocytes and less protein nitration. Our results demonstrate that the cardioprotective function of melatonin is independent of Gpx1.

DOI: 10.1111/j.1600-079X.2008.00654.x

Cite this paper

@article{Chen2009PreventionOI, title={Prevention of ischemia/reperfusion-induced cardiac apoptosis and injury by melatonin is independent of glutathione peroxdiase 1.}, author={Zhongyi Chen and Chu Chang Chua and Jinping Gao and Kao-Wei Chua and Y S Ho and Ronald C. Hamdy and Balvin H. L. Chua}, journal={Journal of pineal research}, year={2009}, volume={46 2}, pages={235-41} }