Melatonin attenuates L-cysteine-induced seizures and lipid peroxidation in the brain of mice.
The effect of melatonin, a potent free radical scavenger, on L-cysteine-induced seizures and lipid peroxidation was investigated in mice. When L-cysteine (1.25, or 5.0 mumol/animal) was injected intracerebroventricularly (i.c.v.) into mice, severe tonic seizures were observed for over 20 sec in 75% and 100% of the treated mice, respectively. However, when melatonin (20 or 100 mg/kg) was injected subcutaneously (sc) into mice 15 min before L-cysteine injection (1.25 mumol/animal, i.c.v.), the incidence of seizures was observed in only 35% and 20% of the treated mice, respectively. Furthermore, when L-cysteine (1.25 or 5.0 mumol/animal, i.c.v.) was injected into mice, lipid peroxidation in whole brain 20 min after injection was significantly increased by 56% or 67% as compared to that of the control. However, when the seizures induced by L-cysteine (1.25 mumol/animal) were abolished by preadministration of melatonin, the increased lipid peroxidation induced by L-cysteine was prevented. These results suggest that there may be a positive correlation between free radical formation and seizures induced by L-cysteine and that melatonin affords protection against the seizures as well as against the associated lipid peroxidation.
Institute of Community Medicine, University of Tsukuba, Ibaraki, Japan.
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Yamamoto
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Tang
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003553:Cystine / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D016166:Free Radical Scavengers; D003553:Cystine; D008315:Malondialdehyde; D008550:Melatonin