Effect of melatonin and phenytoin on an intracortical ferric chloride model of posttraumatic seizures in rats.
The present study was carried out to investigate the effect of melatonin, a potent antioxidant, and phenytoin, a conventional antiepileptic, against FeCl3-induced posttraumatic seizures. Male Wistar rats weighing 200-250 g were implanted with epidural electrodes and allowed to recover. After the recording of baseline EEG, FeCl3 (5 ul, 100 mM) was administered intracortically over a period of 5 min and EEG was monitored for 2 h. Subsequently, rats were sacrificed to estimate oxidative stress, i.e., the amount of malondialdehyde (MDA) in whole brain tissue. A sham group was run parallel with saline (pH adjusted), and a similar protocol for EEG recording and estimation of oxidative stress was followed. FeCl3-treated animals exhibited epileptiform EEG changes (high amplitude sharp waves of increased frequency and polyspikes) within 15 min, which continued throughout the period of observation. MDA levels were found to be significantly elevated as compared to the sham group. Melatonin (50 mg/kg i.p.) administered 30 min before FeCl3 injection delayed the onset of appearance of epileptiform EEG changes, while at a 100 mg/kg dose of there was complete protection, as none of the animal exhibited epileptiform EEG discharge. Brain MDA levels were also significantly reduced in melatonin (50 and 100 mg/kg dose)-treated animals as compared to the vehicle-treated FeCl3-injected rats. In the phenytoin group, all animals showed epileptiform EEG discharge. However, phenytoin at both 50 and 100 mg/kg dose delayed the onset of epileptiform EEG discharge. There were no significant changes in brain MDA levels in the phenytoin-treated group as compared to controls. Melatonin and phenytoin at doses of 100 mg/kg did not show any sign of motor impairment as observed during the rota-rod test. These findings showed a superior protective effect of melatonin over phenytoin in an intracortical FeCl3 model of posttraumatic epilepsy.
Srivastava
A K
AK
Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Gupta
S K
SK
Jain
S
S
Gupta
Y K
YK
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D002712:Chlorides; D004333:Drug Administration Routes; D004569:Electroencephalography; D004834:Epilepsy, Post-Traumatic / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D005260:Female; D005290:Ferric Compounds; D007267:Injections; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D010672:Phenytoin / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D000975:Antioxidants; D002712:Chlorides; D005290:Ferric Compounds; D008315:Malondialdehyde; D010672:Phenytoin; D008550:Melatonin; C024555:ferric chloride