Investigating the time-dependent withdrawal effects of sofosbuvir and/or ribavirin on male mice: a histological and histophotometrical approach

Hepatitis C virus remains a pressing global health issue that has driven extensive research for introducing advanced therapeutic regimens. Among these, the sofosbuvir (SFV)/ribavirin (RBV) drug regimen has had a profound effect on reducing the viral load. Nevertheless, this drug regimen has led to adverse testicular alterations. This study aimed to investigate the restorative effects of SFV/RBV over different durations to determine the possibility of restoring normal histological and histophotometrical testicular tissue. Swiss Albino mice were grouped as total n = 80 with subgroups of n = 5 per timepoint per group, into control group, SFV group received 41mg/kg once daily of SFV, RBV group administered with RBV 41 mg/kg twice daily, and SFV-RBV group received a combined dose of SFV + RBV, identical to those used separately. All drugs were administered by oral gavage for 5 successive days. Testicular tissue in the SFV, RBV, and SFV-RBV groups, at 5 and 70 days after administration, exhibited pronounced alterations, including spermatocyte degeneration, Leydig cell impairment, and disrupted spermatogenesis. Moreover, altered morphometric parameters were observed, characterized by a reduction in testicular area, a diminished seminiferous diameter, and a regression in spermatic epithelium thickness, which collectively contributed to a decline in the spermatogenic index and the conception index. Conversely, starting from day 140 and persisting through day 175 post-treatment, testicular architecture demonstrated substantial recovery, with restoration of spermatogenesis and improvements across morphometric parameters. The administration of SFV and/or RBV for 5 days induced significant testicular injury, which was reversed after 175 treatments. Restorative effects underscore the potential safety of SFV/RBV regimens in human males.