Dose-Dependent Pulmonotoxic Effects of Favipiravir in Rats Biochemical and Histopathological Evaluation

Background and Objective: Favipiravir is associated with more serious side effects at higher doses. This experimental study proposed to investigate the effect of favipiravir on dose-dependent lung toxicity in rats biochemically and histopathologically. Materials and Methods: The rats were divided into four groups as healthy (HG), 100 mg/kg favipiravir (FAV-100), 200 mg/kg favipiravir (FAV-200) and 400 mg/kg favipiravir (FAV-400). Favipiravir 100, 200 and 400 mg/kg doses were administered by oral gavage to the other groups except HG. To the HG group, only distilled water (0.5 mL) was applied in the same way. This procedure was repeated twice a day for a week. Then, the rats were euthanised with high-dose anaesthesia and lung tissues were removed. Oxidative stress parameters such as malondialdehyde (MDA), Total Glutathione (tGSH), superoxide dismutase (SOD), total oxidant status (TOS) and total antioxidant status (TAS) were examined. After the one-way ANOVA, the Tukey's post hoc test was performed. Results: Favipiravir dose-dependently increased MDA and TOS also decreased tGSH, SOD and TAS in rat lung tissue. As favipiravir was given in increasing doses, it was easier to observe the changes between the different groups. This was also supported by the histopathological data. Histopathologically, interstitial pneumonia and lymphoid hyperplasia were mild in the 100 mg/kg favipiravir group, severe at high doses. Conclusion: As the dose of favipiravir increased, oxidant levels increased and antioxidant levels decreased in the lung tissue. In line with these results, it was observed that favipiravir caused a dose-dependent pulmonotoxic effect in rats.