Favipiravir-induced inflammatory and hydropic degenerative liver injury in rats.

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.

Effect of Sunitinib on Liver Oxidative and Proinflammatory Damage Induced by Ischemia-Reperfusion in Rats.

BACKGROUND: Ischemia-reperfusion (IR) injury is defined as a complex pathologic process that begins with the oxygen deprivation of tissue, continues with the production of reactive oxygen radicals (ROS), and expands with an inflammatory response. This study investigates the protective effects of sunitinib, an anticancer drug with demonstrated antioxidant and anti-inflammatory activity, against liver IR damage. Our study aims to investigate the biochemical and histopathologic effects of sunitinib on IR-induced liver damage in rats. METHODS: Albino Wistar male rats were divided into 3 groups: liver IR control (IR), 25 mg/kg sunitinib + liver IR (S+IR), and sham operation (SHAM). RESULTS: In the liver tissue of the IR group, oxidant and proinflammatory cytokine levels such as malondialdehyde, nuclear factor κ B, tumor necrosis factor-α, and interleukin-1ß increased compared with the SHAM and S+IR groups. In addition, antioxidant levels such as total glutathione, glutathione reductase, and glutathione peroxidase were found to be significantly lower in the IR group than in the SHAM and S+IR groups. Although severe histopathologic damage was observed in the IR group, it was evaluated as mild in the S+IR group. The results obtained suggest that sunitinib may be helpful in the treatment of liver IR injury.