Eur J Anat, 23 (6): 393-403 (2019)

Evaluation of testicular cytotoxicity and genotoxicity of sofosbuvir and sofosbuvir - ribavirin in the adult male albino rats

Wael B El-Kholy¹, Manar A Faried¹, Rasha M. Salama¹, Mohammed M. El-Fiky1, Islam El-Garawani²

¹Department of Anatomy and Embryology, Faculty of Medicine, Menoufia University, Egypt, ²Department of Zoology, Faculty of Science, Menoufia University, Egypt

ABSTRACT Hepatitis C is a widely distributed problem all over the world, especially Egypt. Chronically infect-ed people develop serious liver disease and now it is the most common cause for liver transplantation. Recently, a new regimen, sofosbuvir (sovaldi), alone or with combinations as sovaldi-ribavirin, was approved for treating this disease. There are limited studies that explore the effects of these drugs on the reproductive organs, and hence af-fection of male fertility while using these drugs. This study aims to throw more light on whether sovaldi or sovaldi-ribavirin causes testicular dam-aging effects in the adult male albino rats. We in-vestigated the effect of this regimen in a dose equivalent to that used in the human (41 mg/kg once daily orally for sovaldi and 41 mg/kg twice daily orally for ribavirin) for consecutive 5 and 10 days. There was highly significant decrease in tes-tosterone hormone level and marked degenerative changes in the seminiferous tubules and the testic-ular interstitium, with increase in collagen deposits in sovaldi treated rats, and in a more extensive manner in sovaldi-ribavirin treated rats. There was a significant increase of deoxyribonucleic acid (DNA) fragmentation in the treated groups after 10 days. However, there was a non-significant differ-ence in DNA fragmentation in the treated groups after 5 days when compared with control. Immuno-histochemistry detection of caspase-3 showed sig-nificant increase in its expression in the treated groups after either 5 or 10 days. This denoted the specificity of caspase-3 immunohistochemistry technique in the detection of early apoptotic changes. It was concluded that sovaldi and soval-di-ribavirin induced gonadotoxic effects through induction of DNA fragmentation via upregulation of caspase-3, and that the resulting damaging effects increased with longer duration of drug intake.

Keywords: Hepatitis C â?? Sovaldi â?? Sovaldi-ribavirin â?? Testis â?? Apoptosis