Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine-induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress.
Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin.
Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismalia, Egypt. dmon_kamal@yahoo.com
Mona K
MK
Tawfik
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010672:Phenytoin / Q000627:therapeutic use* / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012720:Severity of Illness Index; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy; D013482:Superoxide Dismutase / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000927:Anticonvulsants; D010862:Pilocarpine; D014451:Ubiquinone; D008315:Malondialdehyde; D010672:Phenytoin; D002374:Catalase; D013482:Superoxide Dismutase; C024989:coenzyme Q10; D005978:Glutathione