Silymarin protection role in modulating ribavirin genotoxicity

¿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.¿