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-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.

Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation.

“…Additionally, the drug decreased endogenous antioxidant levels 15 . Similarly, Bilici et al reported that rats treated with a high dose of favipiravir exhibited increased oxidant and decreased antioxidant levels 26 .…”

“…Following the 1-h interval following the administration of drugs and distilled water, favipiravir was orally administered at a dosage of 800 mg/kg twice daily for seven days to all the animal groups except the HG group. Favipiravir is known to cause oxidative and inflammatory damage at high doses 26 . Lacidipine, TPP, and ATP were administered once daily for seven days.…”

Assessment of toxicological effects of favipiravir (T‐705) on the lung tissue of rats: An experimental study

“…[2][3][4][5] Favipiravir has many toxic effects including diarrhea, hepatotoxicity, nephrotoxicity, decreased white blood cell count and neutrophil level, and nausea. [6] Lung tissue is an organ rich in blood supply, and cases of pulmonary intoxication due to drugs have been reported in the literature. [7,8] Not all therapeutic agents could directly cause cell toxicity.…”