Melatonin increases activities of glutathione peroxidase and superoxide dismutase in fetal rat brain

Melatonin is a powerful scavenger of oxygen free radicals. In humans, melat onin is rapidly transferred from the maternal to the fetal circulation. To investigate whether or not maternal melatonin administration can protect th e fetal rat brain from radical-induced damage by increasing the activities of antioxidant enzymes, we administered melatonin to pregnant rats on day 2 0 of gestation. Melatonin (10 mg/kg) was injected intraperitoneally at dayt ime (14:00 hr) and, to remove the fetuses, a laparotomy was performed at 1, 2, or 3 hr after its administration. We measured the melatonin concentrati on in the maternal serum and in fetal brain homogenates and determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px ) in fetal brain homogenates. Melatonin administration markedly increased m elatonin concentrations in the maternal serum and fetal brain homogenates, with peak levels achieved 1 hr after melatonin administration (serum: 538.2 +/- 160.7 pM/mL; brain homogenates: 13.8 +/- 2.8 pM/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in fetal brain ho mogenates increased significantly (P < 0.31). Similarly, SOD activity incre ased significantly between 1 and 2 hr after melatonin administration (P < 0 .01). These results indicate that melatonin administration to the mother in creases antioxidant enzyme activities in the fetal brain and may thereby pr ovide indirect protection against free radical injury. Thus, melatonin may potentially be useful in the treatment of neurodegenerative conditions that may involve excessive free radical production, such as fetal hypoxia and p reeclampsia.