The current study investigated the neuroprotective activity of
idebenone against
pilocarpine-induced
seizures and hippocampal injury in rats.
Idebenone is a
ubiquinone analog with
antioxidant, and
ATP replenishment effects. It is well tolerated and has low toxicity. Previous studies reported the protective effects of
idebenone against
neurodegenerative diseases such as
Friedreich's ataxia and
Alzheimer's disease. So far, the efficacy of
idebenone in experimental models of
seizures has not been tested. To achieve this aim, rats were randomly distributed into six groups. Two groups were treated with either
normal saline (0.9 %, i.p., control group) or
idebenone (200 mg/kg, i.p., Ideb200 group) for three successive days. Rats of the other four groups (P400, Ideb50 + P400, Ideb100 + P400, and Ideb200 + P400) received either saline or
idebenone (50, 100, 200 mg/kg, i.p.) for 3 days, respectively followed by a single dose of
pilocarpine (400 mg/kg, i.p.). All rats were observed for 6 h post
pilocarpine injection. Latency to the first seizure, and percentages of
seizures and survival were recorded. Surviving animals were sacrificed, and the hippocampal tissues were separated and used for the measurement of
lipid peroxides, total
nitrate/
nitrite,
glutathione and DNA fragmentation levels, in addition to
catalase and Na(+), K(+)-
ATPase activities. Results revealed that in a dose-dependent manner,
idebenone (100, 200 mg/kg) prolonged the latency to the first seizure, elevated the percentage of survival and diminished the percentage of pilocapine-induced
seizures in rats. Significant increases in
lipid peroxides, total
nitrate/
nitrite, DNA fragmentation levels and
catalase activity, in addition to a significant reduction in
glutathione level and Na(+), K(+)-
ATPase activity were observed in
pilocarpine group. Pre-administration of
idebenone (100, 200 mg/kg, i.p.) to
pilocarpine-treated rats, significantly reduced
lipid peroxides, total
nitrate/
nitrite, DNA fragmentation levels, and normalized
catalase activity. Moreover,
idebenone prevented
pilocarpine-induced detrimental effects on brain hippocampal
glutathione level, and Na(+), K(+)-
ATPase enzyme activity in rats. Data obtained from the current investigation emphasized the critical role of oxidative stress in induction of
seizures by
pilocarpine and elucidated the prominent neuroprotective and
antioxidant activities of
idebenone in this model.