Melatonin protects fetal rat brain against oxidative mitochondrial damage

Our objective was to investigate the effects of melatonin on the free radic al-induced oxidative damage to mitochondria in fetal rat brain. Female Wist ar rats on day 19 of pregnancy were used. Melatonin (10 mg/kg) or vehicle ( control) was injected intraperitoneally 60 min prior to laparotomy for remo val of the fetuses. The mitochondrial fraction was isolated from the fetal rat brain of each group. Superoxide dismutase (SOD) and glutathione peroxid ase (GSH-Px) activities were measured. As indicators of mitochondrial respi ratory activity, we determined the respiratory control index (RCI) and the adenosine 5-diphosphate/oxygen (ADP/O) ratio in the presence and absence of 2.5 muM hypoxanthine and 0.02 units/mL xanthine oxidase. Mitochondrial lip id peroxidation was determined by measuring the concentration of thiobarbit uric acid reactive substances in fetal brain mitochondria in the presence o r absence of 2.5 muM hypoxanthine. 0.02 units/mL xanthine oxidase, and 50 m uM FeSO4. The free radical-induced rates of inhibition of mitochondrial RCI and the ADP/O ratio were both significantly lower in the fetal rat brains treated with melatonin compared with those of the controls (RCI, 44.25 +/- 15.02% vs. 25.18 +/- 5.86%, P < 0.01; ADP/O ratio, 50.74 +/- 23.05% vs. 13. 90 +/- 7.80%, P < 0.001). The mitochondrial lipid peroxidation induced by f ree radicals was significantly reduced ill the melatonin-treated group comp ared with the controls (484.2 +/- 147.2% vs. 337.6 +/- 61.0%, P < 0.01). Pr etreatment with melatonin significantly increased the activity of GSH-Px (2 0.35 +/- 5.27 to 28.93 +/- 11.01 mU/min mg(-1) protein, P < 0.05) in fetal rat brain mitochondria, but the activity of SOD did not change significantl y. Results indicate that the administration of melatonin to the pregnant ra t may prevent the free radical-induced oxidative mitochondrial damage to fe tal rat brain by a direct antioxidant effect and the activation of GSH-Px.