Investigation of the embryo-toxicity of the antiviral drug “Ribavirin” in Wistar rats during different gestation periods

Abstract

ABSTRACT Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a water-soluble, guanosine nucleoside analog that mimics other purines, including inosine and adenosine. The current study was designed to assess the embryotoxic effect of ribavirin and investigate its teratogenic effect on the placental and fetal liver tissues. In this study, 18 pregnant Wistar rats (165–185 g) 11–13 weeks old were orally administrated ribavirin at a dosage of 82.3 mg/kg at intervals of the organogenesis period (5th −13th) gestation day and fetal developmental period (13th −19th) gestation day. At gestation day 20, the pregnant rats were postmortem, and their fetuses were examined via morphological, histopathological investigations, biochemical analysis, and DNA damage evaluation. The results showed that ribavirin increased the incidence of abortion during the organogenesis period and caused a marked decrease in corrected body weight, uterus, and placenta weight of dams during the fetal developmental period: ribavirin-induced intra-uterine growth retardation, fetal morphological abnormalities, and decreased number of implants/litter. In addition, ribavirin produced histopathological alterations of the placenta and fetal liver tissue, marked elevation of malonaldehyde level, a significant decrease in the activity of antioxidants, and triggered DNA damage. In conclusion, we found that ribavirin has an embryotoxic effect via the generation of free radicals that cause placental DNA damage and altered placental function that affects normal embryo/fetal development.