Light and electron microscopic study on the effect of valproic acid on cerebellar cortex of adult male albino rats and the possible protective effect of L-carnitine

ABSTRACT

Valproic Acid [VPA] is one of the most widely prescribed antiepileptic drugs and is regarded as a first choice for most forms of seizures. Although valproic acid has a wide therapeutic window, yet it is associated with many adverse effects. L-carnitine is a naturally occurring compound widely distributed in all animal cells. It has neurotropic, neuroprotective and antioxidant properties. The aim of the present study was to evaluate the possible neurotoxic effect of valproic acid [Depakene] on the cerebellar cortex of adult male albino rats when used alone and when given concomitantly with L-carnitine. In this study twenty four adult male albino rats were used and divided into four groups [six rats each] Group I was the control group, group II [L-carnitine group] Each animal received 100mg/kg L-carnitine, group III [Valproic acid treated group] Each animal received 50 mg/kg valproic acid and group IV received valproic acid concomitantly with L-Carnitine. Both drugs were given orally once daily for three months. Light microscopic examination of cerebellar cortex of valproic acid treated animals revealed its prominent neurotoxic effect on Purkinje cells and granule nerve cells in association with vacuolation in the molecular layer. Ultrastructural study of the cerebellum of the same group showed dilated Golgi complex and accumulation of secondary lysosomes in association with nuclear shrinkage and irregularity within Purkinje cell perikarya. Many myelinated nerve fibers and nerve cell processes in the molecular and granular layer belonging to the affected nerve cells displayed similar degenerative changes. On the other hand group IV revealed resolving of most of these alterations. However, few Purkinje and granule nerve cells were seen affected in between the normal ones. It could be concluded according to this research that valproic acid has a prominent neurotoxic effect on the cerebellar cortex of the adult male albino rats that can be reduced by concomitant administration of L- carnitine