Apium Graveolens and Rosmarinus Officinalis Protect from Liver Toxicity Induced by Sodium Valproate in Rats and Potentiate its Anticonvulsant Activity on Pentylenetetrazol-Treated Rats
Abstract
Hepatic injury is a dose-limiting side effect of sodium valproate (VPA), a common used drug in the management of numerous nurological disorders, including epilepsy. The present study was designed to investigate the effect of Apium Grafionalies (AG) and Rosmarinus officinalis (RO) against VPA-induced liver injury. Hepatic toxicity was induced by the administration of VPA (500 mg/kg/day) once daily for a period of 7 days. The hepatoprotective group received ethanolic extracts of AG and RO (200 mg/kg/day) for 7 days prior to VPA treatment for seven days. VPA liver toxicity was evaluated based on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and, albumin, and total protein levels as well as by histology. Serum ALT and AST activities were elevated and albumin and total protein levels were depleted. Histopathological changes in liver such as fatty degeneration and focal necrosis were associated with significant increase in TUNEL-positive cells and P53 protein in immunohistochemical study indicating the presence of DNA fragmentation. This biochemical and histological changes were associated with increased oxidative stress damage as evidenced by increases in protein carbonyl (P.Carbonyl) and decreases in total antioxidant capacity (TAC) in liver. These biochemical and histological disturbances were effectively attenuated on pretreatment with either AG or RO extract, which normalized P.Carbonyl and TAC and attenuated histopathological changes…
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