Vitamin D enhances antiepileptic and cognitive effects of lamotrigine in pentylenetetrazole-kindled rats

Abstract

Despite long use of antiepileptic drugs, it remains a challenge to achieve seizure control while reducing adverse effects and preventing cognitive impairment. Several lines of evidence suggest a role of vitamin D in epilepsy. So this study aimed to investigate the effect of vitamin D on epileptogenesis, cognitive dysfunction and antiepileptic activity of lamotrigine, in a rat model of chemical kindling. Rats were kindled by pentylenetetrazole injections every other day over four weeks, together with daily oral treatment by either vehicle, vitamin D, lamotrigine or combination of vitamin D and lamotrigine. The non-treated kindled rats developed generalized seizures and had poor cognitive performance in water maze, associated with prooxidative status; elevated malondialdehyde and nitric oxide with lowered glutathione levels; in brain tissues. Treatment with either vitamin D, lamotrigine or both leads to significant reduction of seizure activity score, improvement of cognitive performance, and amelioration of the disturbed oxidative stress biomarkers. These findings indicate that, vitamin D has anti-epileptic, cognitive improving and antioxidant effects, on its own and enhance the effects of lamotrigine, in a chronic model of epileptic seizures. Thus, vitamin D supplementation may be a useful addition to antiepileptic drugs improving seizure control and cognitive function in patients with epilepsy.