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 brain synaptosomes, KA-induced oxidative stress was measured as shown by significant increases in both the basal generation of reactive oxygen species (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 intrinsic fluorescence of melatonin molecule hindered the evaluation of its protective effect against KA-induced ROS generation. However, melatonin was able to reduce FeSO4/ascorbate-induced ROS generation. The melatonin protective effect was confirmed by in vivo experiments: 73% of rats injected with KA (10 mg/kg i.p.) died within 5 days; melatonin administration i.p. significantly reduced mortality of the animals. The present results suggest that melatonin might be considered a pharmacological agent for the treatment of neurodegenerative pathologies.
Giusti
P
P
Department of Pharmacology, University of Padova, Italy.
Franceschini
D
D
Petrone
M
M
Manev
H
H
Floreani
M
M
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013574:Synaptosomes / Q000187:drug effects
D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C024823:ferric sulfate; D008550:Melatonin; D001205:Ascorbic Acid; D007608:Kainic Acid