Melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in fetal rat brain

We investigated the effects of melatonin on ischemia/reperfusion-induced ox idative damage to mitochondria in fetal rat brain. The utero-ovarian arteri es were occluded bilaterally for 20 min in female Wistar rats on day 19 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing t he occlusion and restoring circulation for 30 min. A sham operation was per formed in control rats. Melatonin (10 mg/kg) or vehicle was injected intrap eritoneally 60 min prior to occlusion. We measured the respiratory control index (RCI) and the adenosine 5-diphosphate (ADP)/oxygen ratio as indicator s of mitochondrial respiratory activity, as well as the concentration of th iobarbituric acid-reactive substances (TBARS) in the mitochondria of fetal brain. Ischemia/reperfusion significantly elevated the concentration of TBA RS and significantly reduced the RCI as well as the ADP/oxygen ratio. Melat onin treatment reversed the ischemia/reperfusion-induced reductions in the RCI (2.29 +/- 0.06-2.64 +/- 0.09, P < 0.05) and in the ADP/oxygen ratio (1. 48 +/- 0.03 - 1.57 +/- 0.02, P < 0.05), and also reduced the elevation in c oncentration of TBARS (11.00 +/- 0.34-7.57 +/- 0.74 nM/mg protein, P < 0.01 ), resulting in values similar to those in untreated, sham-ischemic animals . The results indicate that administration of melatonin to pregnant rats ma y prevent ischemia/reperfusion-induced oxidative mitochondrial damage in fe tal rat brain.