Favipiravir-induced inflammatory and hydropic degenerative liver injury in rats

Adv Clin Exp Med. 2023 Aug;32(8):881-887. doi: 10.17219/acem/159089.

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.

Material 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-κB) 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.

Keywords: favipiravir; hydropic degeneration; inflammation; rat.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • COVID-19*
  • Glutathione / metabolism
  • Liver
  • Oxidative Stress*
  • Rats
  • Rats, Wistar

Substances

  • favipiravir
  • Glutathione
  • Antioxidants