doi: 10.1111/j.1472-8206.2008.00654.x ORIGINAL ARTICLE Hepatoprotective effects of misoprostol and silymarin on carbon tetrachloride-induced hepatic damage in rats Omar M.E. Abdel Salam a *, Amany A. Sleem a , Enayat A. Omara b , Nabila S. Hassan b a Department of Pharmacology, National Research Centre, Tahrir St, Dokki, Cairo, Egypt b Department of Pathology, National Research Centre, Tahrir St, Dokki, Cairo, Egypt INTRODUCTION Presently, very few therapies are available for treatment of chronic liver disease especially that caused by the hepatitis C virus (HCV) infection. Today’s standard therapy for treating patients with chronic HCV infection is the combination of pegylated interferon and ribavirin with the aim of preventing progressive hepatic fibrosis by eradicating the virus RNA [1]. This combination therapy can result in virus elimination and substantial histolog- ical improvement in approximately 55% of patients [2,3]. Relapse, however, occurs in a significant number of cases, while serious side-effects preclude the use of this form of therapy in a substantial proportion of patients. In this context, it has been reported that from 10% to 14% of participants in the registration trials for combination therapy involving the pegylated interferon withdrew prematurely from therapy because of adverse events [4,5]. Apart from interferon and ribavirin therapy, silymarin, a standardized extract, derived from the milk Keywords acute hepatic injury, misoprostol, silymarin, rat Received 22 April 2008; revised 11 August 2008; accepted 26 September 2008 *Correspondence and reprints: omasalam@hotmail.com ABSTRACT The aim of this study was to investigate the effect of misoprostol, silymarin or the co- administration of misoprostol + silymarin on the carbon tetrachloride (CCl 4 )-induced hepatic injury in rats. Misoprostol (10, 100, 1000 lg/kg), silymarin (25 mg/kg) or misoprostol (100 lg/kg) + silymarin (25 mg/kg) was given once daily orally simultaneously with CCl 4 and for 15 days thereafter. The results showed that misoprostol (10, 100 or 1000 lg/kg) conferred significant protection against the hepatotoxic actions of CCl 4 in rats, reducing serum alanine aminotransferase (ALT) levels by 24.7%, 42.6% and 49.4%, respectively compared with controls. Miso- prostol, given at 100 or 1000 lg/kg, decreased aspartate aminotransferase (AST) by 28 and 43.6% and alkaline phosphatase (ALP) by 19.3% and 53.4% respectively. Meanwhile, silymarin reduced ALT, AST and ALP levels by 62.7%, 66.1% and 65.1% respectively. The co-administration of misoprostol (100 lg/kg) and silymarin (25 mg/kg) resulted in 61.4%, 66.1% and 57.5% reduction in ALT, AST and ALP levels respectively. Histopathological alterations and depletion of hepatocyte glycogen and DNA content by CCl 4 were markedly reduced after treatment with misoprostol, silymarin or misoprostol + silymarin. Image analysis of liver specimens revealed a marked reduction in liver necrosis; area of damage: 32.4%, 24% and 10.2% after misoprostol (10, 100 or 1000 lg/kg), 7.2% after silymarin and 10.9% after treatment with misoprostol 100 lg/kg + silymarin, compared with CCl 4 control group (46.7%). These results indicate that treatment with misoprostol protects against hepatocellular necrosis induced by CCl 4 . This study suggests a potential therapeutic use for misoprostol in liver injury. ª 2009 The Authors Journal compilation ª 2009 Socie ´ te ´ Franc ¸aise de Pharmacologie et de The ´ rapeutique Fundamental & Clinical Pharmacology 23 (2009) 179–188 179