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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                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200980 with subgroups of\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095 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\u2009+\u2009RBV, 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.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-04974-x","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T01:26:39Z","timestamp":1770081999000},"page":"10421-10437","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the time-dependent withdrawal effects of sofosbuvir and\/or ribavirin on male mice: a histological and histophotometrical approach"],"prefix":"10.1007","volume":"399","author":[{"given":"Esraa H.","family":"Shahat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamza Ahmed El","family":"Shabaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elham H. 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