IN-VITRO AND IN-VIVO PROTECTION AGAINST KAINATE-INDUCED EXCITOTOXICITY BY MELATONIN

In this study, the protective effect of melatonin against kainate (KA) -induced neurotoxicity was evaluated in vitro and in vivo. In rat brai n synaptosomes, KA-induced oxidative stress was measured as shown by s ignificant increases in both the basal generation of reactive oxygen s pecies (ROS), assessed by a fluorescent method, and lipid peroxidation , evaluated as malondialdehyde (MDA) levels. Melatonin decreased, in a concentration-dependent manner, KA-induced lipid peroxidation. The in trinsic fluorescence of melatonin molecule hindered the evaluation of its protective effect against KA-induced ROS generation. However, mela tonin was able to reduce FeSO4/ascorbate-induced ROS generation. The m elatonin protective effect was confirmed by in vivo experiments: 73% o f rats injected with KA (10 mg/kg i.p.) died within 5 days; melatonin administration i.p. significantly reduced mortality of the animals. Th e present results suggest that melatonin might be considered a pharmac ological agent for the treatment of neurodegenerative pathologies.