The effects of ascorbic acid on penicillin-induced epileptiform activity in rats.
OBJECTIVE
Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as alpha-tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin-induced epileptiform activity.


METHODS
A single microinjection of penicillin (2.5 microl, 500 units, intracortically) into the left sensorimotor cortex induced epileptiform activity within 2-5 min, progressing to full seizure activity lasting approximately 3-5 h. In the first set of experiments, 30 min after penicillin injection, six different doses of ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered intraperitoneally (IP). The other group of animals received the effective dose of ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was stopped 24 h before penicillin treatment. Another group of rats received the effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin treatment. In the second set of experiments, the lipid peroxidation (MDA) and reduced glutathione (GSH) levels of brain were measured in the control, control + ascorbic acid, penicillin, and penicillin + ascorbic acid groups.


RESULTS
Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin injection), decreased both the frequency and amplitude of penicillin-induced epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400 mg/kg, 30 min after penicillin injection), decreased the frequency of epileptiform activity without changing the amplitude. Ascorbic acid, at the lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin injection), did not change either the frequency or amplitude of epileptiform activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose in changing the frequency and amplitude of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin treatment caused a significant delay in the onset of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did not change the latency of epileptiform activity. The most effective dose of ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the increase in lipid peroxidation level (MDA) occurring after penicillin-induced epileptiform activity.


CONCLUSIONS
These data indicate that ascorbic acid has neuroprotective activity against penicillin-induced epileptiform electrocorticogram activity.
Ayyildiz
Mustafa
M
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey.
Coskun
Sule
S
Yildirim
Mehmet
M
Agar
Erdal
E
D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D004827:Epilepsy / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation; D008297:Male; D010406:Penicillins; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D010406:Penicillins; D005978:Glutathione; D001205:Ascorbic Acid