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

: 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 × heart rate) was exacerbated in mice deficient in Gpx1 (51 ± 3% for Gpx1+/+ mice versus 31 ± 6% for Gpx1−/− mice, P