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In vitro and in vivo protection against kainate‐induced excitotoxicity by melatonin
Author(s) -
Giusti Pietro,
Franceschini Davide,
Petrone Marcella,
Manev Hari,
Floreani Maura
Publication year - 1996
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1996.tb00263.x
Subject(s) - melatonin , lipid peroxidation , in vivo , oxidative stress , reactive oxygen species , malondialdehyde , neurotoxicity , kainate receptor , excitotoxicity , chemistry , pharmacology , kainic acid , in vitro , medicine , luzindole , endocrinology , biochemistry , biology , melatonin receptor , toxicity , apoptosis , glutamate receptor , programmed cell death , microbiology and biotechnology , receptor , ampa receptor
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 FeSO 4 /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.