Melatonin protects against ischemia and reperfusion-induced oxidative lipid and DNA damage in fetal rat brain

To investigate whether melatonin reduces the susceptibility of the fetal ra t brain to oxidative damage of lipids and DNA, we created a model of fetal ischemia/reperfusion using rats at day 19 of pregnancy. Fetal ischemia was induced by bilateral occlusion of the utero-ovarian artery for 20 min. Repe rfusion was achieved by releasing the occlusion and restoring the circulati on for 30 min. A sham operation was performed in control rats. Melatonin (1 0 mg/kg) or vehicle was injected intraperitoneally 60 min prior to the occl usion. We measured the concentration of thiobarbituric acid reactive substa nces (TBARS) in fetal brain homogenates, as well as the levels of deoxyguan osine (dG) and 8-hydroxydeoxyguanosine (8-OHdG) in DNA extracted from those homogenates. Ischemia for 20 min did not significantly alter the levels of dG, 8-OHdG, and TEARS. Subsequent reperfusion, however, led to a significa nt reduction in the dG level (P < 0.05) and to significant increases in the levels of 8-OHdG (P < 0.05) and TEARS (P < 0.05), and in the 8-OHdG/dG rat io (P < 0.005). Melatonin administration prior to ischemia significantly re duced the ischemia/reperfusion-induced increases in the levels of 8-OHdG (1 4.33 +/- 6.52-5.15 +/- 3.28 pmol/mg of DNA, P < 0.001) and TEARS (11.61 +/- 3.85-4.73 +/- 3.80 nmol/mg of protein, P < 0.001) as well as in the 8-OHdG /dG ratio (7.19 +/- 2.49-1.61 +/- 0.98, P < 0.001). Furthermore, melatonin significantly increased the dG level (210.19 +/- 49.02-299.33 +/- 65.08 nmo l/mg of DNA, P < 0.05). Results indicate that melatonin administration to t he pregnant rat may prevent the ischemia/reperfusion-induced oxidative lipi d and DNA damage in fetal rat brain.