Apium graveolens modulates sodium valproate-induced reproductive toxicity in rats

Sodium valproate (VPA), a common treatment of epilepsy and other diseases, is known to have severe toxic effects on testis both in experimental animals and in humans. The present study was designed to investigate the protective effect of Apium graveolens (AG) against the VPA-induced testis injury. Testicular toxicity was induced by the administration of VPA (500 mg/kg/day) once daily for 7 consecutive days. Protective group received daily doses (200 mg/kg/day) of AG crude extract for 23 days prior to VPA administration. VPA-induced reproductive toxicity was assessed based on the weight of testes, sperm analysis, and serum concentrations of sexual hormones. The relative weights of testes and epididymes and the sperm numbers viability were all decreased following the valproate administration. Testosterone levels dropped while follicle stimulating hormone (FSH) level increased following the drug administration. Severe histopathological changes in testis were observed such as degeneration of seminiferous tubules and depletion of germ cells. These biochemical and histological changes were also associated with alterations of oxidative stress markers. Levels of malondialdehyde have increased, while superoxide dismutase activity has decreased. Pretreatment with A. graveolens extract has effectively alleviated most of the VPA-induced effects suggesting a protective role of A. graveolens extract against experimental VPA-induced toxicity. Apigenin content was estimated and was shown as a major fraction of the A. graveolens extract.