Anticonvulsant effects of 1, alpha-hydroxy-vitamin D in comparison to the conventional antiepileptic drug phenytoin in the pilocarpine model of epilepsy in rats

ABSTRACT

Conventional antiepileptic drugs fail to adequately control seizures and exhibit unfavorable side effects. Vitamin D3 [Cholecalciferol], has its essential role in calcium and phosphorus metabolism, and is involved in regulating the functions of the central nervous system. Moreover, it has long been known that chronic treatment with antiepileptic drugs impairs mineral homeostasis in epileptic patients, leading to marked hypocalcaeinia and reduced plasma levels of vitamin D which in turn may increase seizure]. to test the possible role of the neurosteroid hormone 1, alpha-hydroxy vitamin D3 [1, alpha vit. D3], an active form of Vitamin D3 in epilepsy and its interactions with the conventional antiepileptic drug phenytoin in the pilocarpine induced seizures in rats two experiments were performed. Experiment 1 was conducted to measure seizures severity, oxidative markers and calcium level in the pilocarpine model of epilepsy live groups of rats were used. 1-Control group received saline intraperitoneal [i.p.] only, 2-control epileptic group received pilocarpine 320 mg/kg i.p., 3-vitamine D3 treated group received 1, alpha-H vit. D3 40 ng/kg i.p. one hour before pilocarpine, 4-Phenytoin treated group received 11.2mg/kg phenytoin i.p., 2 hours before pilocarpine and 5-both 1, alpha-H vit. D3 and phenytoin treated group in the same doses mentioned before. Experiment 2 was conducted to test the effect of chronic treatment for one week with 1, alpha-H vit. D3, phenytoin or both on oxidative markers, calcium level and behavioral tests in rats. Overall, compared to the saline-treated control animals, the 1, alpha-H vit. D3 -treated rats demonstrated reduced severity of pilocarpine induced seizures, with decreased levels of oxidative markers. Co-administration of 1, alpha-H vit. D3 with phenytoin resulted in a significant reduction of seizure severity and duration. Furthermore, 1.alpha-H vit. D3 potentiated the anticonvulsant activity of phenytoin and reduced its undesirable effects as regard increase in oxidative markers and memory impairment that were induced by phenytoin. These findings show that Vitamin 0 plays a direct anticonvulsant role in the brain and suggest that the Vitamin D may represent a new anticonvulsant drug increasing the efficacy of conventional antiepileptic drugs