Adverse effects of therapeutic doses of sofosbuvir and ribavirin on the liver of the developing mice embryos

Abstract

The aim of this study was to investigate the adverse effect of Sofosbuvir (SFV) and / or Ribavirin (RBV) on developing mice embryos in order to determine the morphological and the liver tissue alterations of mice fetuses. The pregnant mice were divided into eight groups: 1) control group (GI); 2) SFV 1.64 mg/mouse/day (GII); 3) SFV 4.93 mg/mouse/day (GIII); 4) RBV 0.2065 mg/mouse/day (GIV); 5) RBV 0.856 mg/mouse/day (GV); 6) SFV 1.64 mg/mouse/day and RBV 0.856 mg/mouse/day (GVI); 7) SFV 4.93 mg/mouse/day and RBV 0.856 mg/mouse/day (GVII) and 8) SFV 1.64 mg/mouse/day and RBV 0.2065 mg/mouse/day (GVIII). Maternal exposure of both drugs SFV and/or RBV affected the body weight, number of fetuses and presence of resorption sites. A variety of morphological abnormalities were detected in all groups demonstrating several craniofacial malformations and conspicuous congenital malformations. The most pronounced effects in (GV) were the detection of exencephaly and facial condition. The liver of the maternally treated fetuses of (GII) and (GIV) revealed necrotic hepatocytes with vacuolated cytoplasm. While (GIII) and (GV) revealed hepatocytes degeneration, damaged endothelial cells lining the central veins and the presence of activated Kupffer cells.