Evaluation of the effects of favipiravir (T-705) on the lung tissue of healty rats: An experimental study

Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor widely used during the COVID-19 pandemic, effectively reduces viral load but has been linked to inflammatory changes in tissues such as the liver and kidneys. High-dose and prolonged use of favipiravir for COVID-19 raises concerns about its potential toxic effects on the lungs, particularly in patients with pre-existing pulmonary conditions. This study investigated favipiravir's effects on lung tissue in healthy rats. Experimental groups included a Control (saline) and three favipiravir doses: Low (200 mg/kg/day loading, 100 mg/kg/day maintenance), Medium (400 mg/kg/day loading, 200 mg/kg/day maintenance), and High (600 mg/kg/day loading, 300 mg/kg/day maintenance), all administered via gavage for 10 days. Histopathological analysis showed normal lung structure in the Control group, while favipiravir-treated groups exhibited Bronchus-Associated Lymphoid Tissue (BALT) enlargement, inflammation, fibrosis, and hemorrhage. Immunohistochemical analysis revealed dose-dependent increases in TNF-alpha, TGF-(3, IL-6, IFN-gamma, IL1-(3, alpha-SMA, and collagen-1, especially in the High-dose group (p < 0.05). These findings suggest favipiravir may induce lung inflammation and fibrosis, emphasizing the need for careful evaluation of its safety in clinical settings, particularly for COVID-19 treatment. Future research should investigate the underlying mechanisms of these effects with clinical studies to assess their relevance to humans, high-risk pulmonary patients.