The protective effects of melatonin from oxidative damage induced by amyloid beta-peptide 25-35 in middle-aged rats.

Abstract

This work investigated the ability of melatonin to prevent oxidative damage in brain tissue induced by injection of beta-amyloid peptide 25-35 (Abeta25-35) in middle-aged rats. The Morris water maze was used to evaluate the cognitive function of the rats. Thiobarbituric acid-reactive substances and antioxidative enzymes (superoxide dismutase and glutathione peroxidase) activities were measured. It was found that injection of (Abeta25-35) (20 microg) into the rat hippocampus caused an increase in the latency (the time to find the platform), the total swimming distance to the platform, and the starting angles in (Abeta25-35)-treated rats. Furthermore, a significant rise in lipid peroxidation and decrease in antioxidative enzyme activities in brain tissue were found. Melatonin (0.1, 1, and 10 mg/kg, i.g. x 10 days) improved the spatial resolution of amnesic rats in the Morris water maze test. Meanwhile, melatonin antagonized the lipid peroxidation in both the mitochondria (P < 0.01) at the doses of 0.1, 1.0, and 10 mg/kg and in the cytoplasm at the doses of 0.1 and 1.0 mg/kg. Also in the amnesic rats, melatonin (0.1, 1.0, and 10 mg/kg. i.g. x 10 days) stimulated the antioxidative enzyme activities. The results show that melatonin effectively reduced lipid peroxidation and enhanced the antioxidative enzyme activities in Abeta(25-35)-treated rats, which may contribute to the improvement of rats' learning and memory impaired by Abeta(25-35).