الفهرس 
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Abstract
Summary
Hepatitis C virus (HCV) can cause both acute and chronic hepatitis, ranging from mild to severe lifelong illness. Around 180 million people worldwide suffer from chronic viral hepatitis C infection. The infected persons are often unaware of it due to the slow progression of liver diseases with few or no symptoms, so don’t seek prevention, care, or treatment. Studies project a marked increase in the incidence of cirrhosis, decompensated cirrhosis and hepatocellular carcinoma over the next 10 to 20 years.
Sofosbuvir approved for the treatment of chronic hepatitis C on 6 December 2013, by the Food and Drug Administration ( FDA ) as antiviral therapy with HCV genotype1,2,3 or 4 infections, including hepatocellular carcinoma patients meeting Milan requirements (waiting for liver transplantation) and HCV / HIV-1 co-infection patients. It is a specific HCV NS5B polymerase nucleotide analogue inhibitor which acts as a false substratum for RNA-dependent polymerase and ends at chain termination after incorporation into the newly formed RNA chain. This medicines produce higher sustained virological reactions (SVRs) than interferon-based regimens, are shorter in length of treatment, are administered orally, and have less side effects. It must be used in conjunction with at least one other DAA.
The use of sofosbuvir / ribavirin combination has been shown to be effective in preventing relapses and viral breakout, which can lead to higher rates of SVR. While ribavirin has been investigated for multiple viral infections as a therapy, its primary application was in the treatment of chronic HCV infection, having obtained FDA approval for this indication in 1998.
Silymarin is a natural antioxidant derived from the plant silybum marianum from the seeds and fruits of milk thistle. Silymarin recovery of various liver disorders, develop efficacy in restoring liver function and liver cell regeneration.
The aim of this study is evaluating the protective effect of Silymarin as a natural product against the side effects of sofosbuvir and ribavirin as an antiviral agents used to treat HCV on the genetic material of mice. We use cytogenetic methods for determining:-Chromosome aberrations, Mitotic index and Sperms abnormalities (head-tail).Molecular studies for determining the BCL2, Bax and Caspase3 mRNA expression level by using RT-PCR.
Results show that, sofosbuvir and ribavirin cause chromosome aberration to the structure. Circle, deletion, fragmentation of chromatids, centromeric attenuation, centromeric fusion, and end to end were observed. Also, Sofosbuvir and ribavirin decrease the rate of death-inducing cell division. we found that nearly all groups that injected silymarin either before or after or with the drug cause chromosomal abbarism to decrease.
The findings also revealed that Sofosbuvir and ribavirin cause head abnomalies such as without hook, banana, amorphous and hammer form head of mice sperm. When silymarin injected, we notice reduction in sperm abnormalities.
In our research, we found that sofosbuvir and ribavirin induces overexpression of the genes Bax and caspase3 while causing a decrease in the expression of the gene BCL2. These results report that cell apoptosis is induced by Sofosbuvir and ribavirin.