الفهرس | Only 14 pages are availabe for public view |
Abstract Hepatitis C is an infectious disease caused by HCV that primarily affects the liver. An Egyptian demographic health survey conducted in 2008 concluded that 14.7% of the population have been infected, making this the highest prevalence in any population in the world. The treatment of HCV patients has been changed with the development of Sofosbuvir which is uridine nucleotid analog. A dose of 400 mg of Sofosbuvir has been found to be most effective, with treatment durations ranging from 12 to 24 weeks, in various combinations of pegylated interferon and ribavirin. According to the literature, patients with HCV are associated with poor semen quality and hormonal disturbances. So, it will be of interest to explore if the Sofosbuvir has any negative influences on the testicular functions particularly that the HCV patients are already associated with some degree of testicular dysfunction. Therefore, the current study aimed to evaluate the potential effects of Sofosbuvir on testicular functions in male rats in an experimental study; especially there is no previous data about its effects in clinical studies. The study included thirty adult male albino rats weighing 200-300 g They were randomly divided into 3 groups: group (1): Controls; group (2): Rats received oral Sofosbuvir 40 mg/kg/day for 12 weeks; group (3): Rats received oral Sofosbuvir 80 mg/kg/day for 12 weeks. The effects of SofosbuvirSummary and conclusion 76 on testicular functions are evaluated through: testicular size; semen parameters; hormonal profile (Total testosterone, FSH, LH, and Prolactin); and histopathological evaluation of testicular tissue with (H&E) stain. The current study demonstrated a statistical significant difference of the relative testicular weight (gonadosomatic index), being lower in SOF-H as compared to SOF-L. Also, H&E stained testicular slides showed a significant reduction of seminiferous tubules diameter (STD); germinal epithelium height (GEH); tubular differentiation index (TDI) and spermiogenesis index (SPI) in both SOF-L and SOH-H groups as compared to control; with a more significant reduction in SOF-H as compared to SOF-L. In addition, the current study showed a significant reduction of both sperm concentration and motility in SOF-L and SOF-H as compared to control with no significant changes between SOF-L and SOF-H. Also it showed pituitary hormones changes with FSH and LH were significantly reduced in both SOF-L and SOF-H as compared to control with no significant changes between them. Total testosterone was significantly reduced only in SOF-L as compared to control. Prolactin was significantly increased in SOF-L and decreased in SOF-H as compared to control. The current study concluded that Sofosbuvir has a negative effect on the pituitary- testicular functions of the rats. Groups with larger sample size are needed. Also, a recovery group is needed to evaluate the long term effectsSummary and conclusion 77 after SOF stoppage. Although a potential pituitary- testicular dysfunction has been associated with SOF administration especially in high dose, the exact mechanism of this dysfunction has not been studied. Further studies evaluating oxidative stress indices in semen and testicular tissue will be beneficial. |