Memorial Symposium at Royal Society of Medicine, London, September 13 1997: Both melatonin and a putative nuclear melatonin receptor agonist CGP 52608 stimulate glutathione peroxidase and glutathione reductase activities in mouse brain in vivo

Melatonin is both a direct and indirect antioxidant. Thus, it scavenges a variety of free radicals and it stimulates the antioxidative enzyme glutathione peroxidase. Melatonin has been shown to enter the brain and to accumulate in the nucleus of cells. A high-affinity nuclear binding site/receptor for melatonin has been tentatively identified. Using an agonist of the putative nuclear receptor, we show here that the agonist duplicates the stimulatory effect of melatonin on cerebral and cerebellar glutathione peroxidase activity in vivo. We also report that both melatonin and the agonist stimulate glutathione reductase activity. The increases in both enzyme activities are time dependent, but the stimulation in glutathione reductase activity is delayed compared to that of glutathione peroxidase. The results indicate that melatonin's ability to protect the brain from oxidative damage may be in part be a consequence of a receptor-mediated stimulation of neural antioxidative enzymes.