Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation.
OBJECTIVE
Intracortical injection of iron ion induces recurrent seizures and epileptic discharges in the electrocorticogram. This observation may be used as a model of posttraumatic epilepsy. The involvement of iron-mediated oxygen free radical species and neuronal lipid peroxidation in iron-induced seizure has been suggested. Melatonin exerts free radical scavenging properties. In this study, we examined the protective effect of melatonin against iron-induced seizures.


METHODS
We examined the protective effect of melatonin against in vitro iron-induced oxidative damage in homogenates from rat cerebral cortex, by measuring the concentration of thiobarbituric acid reactive substances (TBARS), as an index of oxidative damage. We also examined the effect of melatonin on the appearance of epileptic discharges in the EEG following injection of FeCl3 into the sensorimotor cortex in anesthetized rats, and by measuring the concentration of TBARS in the brain tissue.


RESULTS
FeCl3 increased the concentration of TBARS in brain homogenates in a concentration-dependent manner, and melatonin reduced FeCl3-induced rise in TBARS in a dose-response fashion. Pretreatment with melatonin suppressed or delayed the development of FeCl3-induced epileptic discharges and decreased the concentration of TBARS in brain tissues.


CONCLUSIONS
Our results suggest that iron ion generates oxygen free radical species that induce neuronal macromolecular peroxidation and seizure, and that melatonin inhibits iron-induced seizures by scavenging free radicals.
Kabuto
H
H
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Japan.
Yokoi
I
I
Ogawa
N
N
D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002712:Chlorides; D004569:Electroencephalography / Q000187:drug effects; D004834:Epilepsy, Post-Traumatic / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism
D002712:Chlorides; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D007501:Iron; D008550:Melatonin; C024555:ferric chloride