Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation

Purpose: Intracortical injection of iron ion induces recurrent seizures and epileptic discharges in the electrocorticogram. This observation may be used as a model of post traumatic 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.