Favipiravir-Induced Inflammatory and Hydropic Degenerative Liver Injury in Rats

Abstract

Background. Favipiravir is very effective in the treatment of many viral infections, especially at high doses. It was used at such doses to treat coronavirus disease 2019 (COVID-19) during the pandemic. However, liver damage was reported in patients undergoing such treatment. Objectives. This study aimed to investigate the effects of low and high doses of favipiravir on the liver of rats, using biochemical and histopathological methods. Materials and methods. Wistar albino rats were allocated to one of 3 groups, namely a healthy group (HG), a 100 mg/kg favipiravir (FAV-100) group and a 400 mg/kg favipiravir (FAV-400) group. Favipiravir was administered orally at 100 mg/kg and 400 mg/kg doses to the FAV-100 (n = 6) and FAV-400 (n = 6) groups, respectively. Distilled water was administered orally (1 mL) using the same method to the HG (n = 6). This procedure was repeated twice a day for 1 week. At the end of this period, the animals were euthanized with a high dose of thiopental anesthesia (50 mg/kg) and their liver tissues were removed. Results. Favipiravir caused an increase in malondialdehyde (MDA), nuclear factor kappa B (NF-kappa B) and interleukin 6 (IL-6) levels in the liver tissue, as well as elevated alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) levels in the blood. Moreover, favipiravir caused a decrease in total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. In addition, severe edema, lymphocyte infiltration and hydropic degeneration were observed in the liver tissue of the FAV-400. Conclusions. High-dose favipiravir caused more significant oxidative and inflammatory damage in the liver tissue of rats than low-dose favipiravir.