Mechanism of cytotoxicity of ribavirin in the rat bone marrow and testis.

Mechanisms of cytotoxicity of an antiviral drug, ribavirin was studied in the rat bone marrow and testis. Ribavirin at the dose levels of 20, 100 and 200 mg/kg was treated (i.p.) either as single (for bone marrow) or 5 (for testis) treatments. Bone marrow smears were obtained at 24, 48 and 72 h following the exposure and stained with the May-Gruenwald-Giemsa combination. Smears were screened for the incidence of dead cells, and at 24 h, a total of 2000 erythrocytes were counted to obtain the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs) (P/N). Step 19 spermatids/stage VII tubule, dividing cells (meiotic figures)/stage XIV tubule and the incidence of tubules with dead cells were counted in periodic acid--Schiff's reaction and haematoxylin (PAS-H) stained testicular sections on days 14, 35, 70 and 105. Significant decrease in the step 19 spermatids and meiotic figures, and increase in the incidence of tubules with dead cells (P < 0.05-0.01) were observed mainly on days 14 and 35. The cell death was observed in the bone marrow mainly at the two higher dose levels and significant decrease (P < 0.001) in P/N ratio was observed. This present study concludes that the cytotoxicity of ribavirin in these two target cell-lines in due to the induction of cell death and prevention of the cell division.