reproductive toxicity of ribavirin in the adult rabbit testis [light and electron microscope study]

ABSTRACT

Ribavirin is one of the approved antiviral drugs indicated for various viral infections. So it is used as a current chemotherapy with interferon alpha for treatment of viral hepatitis C. The aim of the present study was to assess Ribavirin toxicity on the structure of testicular tissue of adult male rabbits after exposure to the drug as well as to evaluate the extent of improvement of testicular tissue structure after stoppage of drug administration. Eighteen adult male rabbits were used in this study. The rabbits were divided into three groups control group [C] 6 male rabbits received distilled water by the same method and duration as the corresponding experimental groups, a treated group [T] was formed of 6 adult rabbits receiving Ribavirn in a dose of 15mg/kg/day at two divided doses for 10 weeks and a recovery group [R] receiving Ribavirin in a dose of 15mg/kg/day for 10 weeks followed by 10 weeks without treatment to assess the effect of drug withdrawal. The testes of each rabbit were immediately dissected out and specimens were fixed and stained with H and E. Minute specimens were stained with Toluidine blue for LM examination, and ultrathin sections were stained with Uranyl acetate and Lead citrate for TEM examination. Marked histological changes of the testis at the level of the light and electron microscope including disorganization of the semineferous tubules, reduction in the thickness of the germinal epithelium vaccuolation and degeneration of the spermatogenic cells. Sertoli cells and leydig cells were also affected. Partial recovery of the testis was observed in the recovery group, but some of the changes were still obvious. These testicular changes persisted after stoppage of Ribavirin administration indicates the cumulative toxic effects of Ribavirin that lead to hypospermatogenesis, oligospermia and then azospermia