The genotoxic and cytotoxic effects of ribavirin in rat bone marrow

The genotoxic and cytotoxic effects of the antiviral drug, ribavirin, was studied in rat bone marrow by employing the micronucleus assay. Ribavirin in doses of 10, 15, 20, 30, 50, 75, 100 and 200mg/kg, and cyclophosphamide (CP) 40mg/kg (only for sex-difference study) were injected intraperitoneally. Bone marrow was collected at 24h and 48h following the injection. To evaluate the recovery, the bone marrow was also sampled at 72h from 20, 100 and 200mg/kg treated rats. The micronucleus assay was conducted according to the standard procedure. Ribavirin elevated the incidence of micronuclei (except 10mg/kg) in erythrocytes (P<0.01). The micronucleated polychromatic erythrocytes showed the initial steep increase at 15 and 20mg/kg dose level, then with the gradual increase, possibly due to the limited metabolism and action of higher doses. The incidence of micronucleated normochromatic erythrocytes was not dose dependent. The effect was more at 48h than 24h due to prolonged toxicity of the drug or its metabolites, and by 72h, recovery was observed eventhough the genotoxicity was significant. The PCE% decreased as the dose was increased up to 75mg/kg, then without much difference between two higher doses. Only 100mg/kg ribavirin and CP showed more toxicity on male rats. Cytotoxicity was seen due to hindered erythropoiesis or cell destruction. Our findings suggest that ribavirin is genotoxic and cytotoxic agent for rat bone marrow.