Abstract
Background Favipiravir was widely used to treat coronavirus disease 2019 (COVID-19) early in the pandemic. Later, many reports began to be published about the side effects of favipiravir on different tissues. However, the side effects of favipiravir on the oral and nasal mucosa remain unknown. This experimental study aimed to evaluate the pathological effects of favipiravir on the oral-nasal mucosa and investigate whether vitamin C (Vit C) reduces these lesions in old and young rats. Methodology A total of 100 rats were used for this study. The rats were administered favipiravir (20 mg/kg and 100 mg/kg) and Vit C (150 mg/kg/day) for 14 days. At the end of the study, rats were euthanatized, and oral-nasal mucosal histopathological changes were evaluated. Nuclear factor kappa-ligand (RANKL) and caspase-3 expressions were immunohistochemically examined. Results Favipiravir caused severe lesions in old rats compared to young, and the severity of the lesions increased with the dosage. Severe hyperemia and erosive-ulcerative lesions were observed in the oral-nasal mucosa. In addition, increased RANKL and caspase-3 expressions were observed in a dose-dependent manner. In both young and old groups, Vit C treatment showed decreased caspase-3 and RANKL expression; a more prominent decrease was seen in young rats. Conclusions This study showed that favipiravir could cause histopathological lesions in the oral and nasal mucosa. However, the administration of Vit C with favipiravir can provide a protective effect against this damage. The curative effect of Vit C was more pronounced in young rats and at low doses.