Silymarin Protection Role in Modulating Ribavirin Genotoxicity : Evaluation of the antioxidant silymarin role in ¿modulating the in vivo genotoxicity of the antiviral drug ¿ribavirin

Hepatitis C virus (HCV), first described in 1989, is now recognized as one of the main causes of chronic liver disease worldwide. HCV infection becomes chronic in the majority of cases. All current treatment protocols for hepatitis C are based on the use of interferon alpha and ribavirin (RBV). Despite RBV broad spectrum in treatment of various viral infections, recently several reports revealed genotoxic effects of RBV in vivo and in vitro. This genotoxicity was correlated with the production of reactive oxygen species (ROS). This study aimed to evaluate RBV genotoxicity and investigate the role of the natural antioxidant silymarin (SL) to modulate RBV genotoxicity. In the present study, RBV was injected i.p. at three dose levels either as a single injection or multiple injections for 5 consecutive days. Other groups were treated with SL (70 mg/kg)1hr before RBV injection. Mice were sacrificed at different sampling time after RBV treatment. Micronucleus (MN) and SSCP assays were used as cytogenetic assay and molecular end point to assess genotoxic and cytotoxic effects of RBV and to evaluate SL pretreatment protection effect.