Investigation of oxidative, inflammatory and apoptotic effects of favipiravir use alone and combined with vitamin C on brain tissue of elderly rats

Favipiravir is a nucleoside analogue antiviral drug and inhibits the replication of many RNA viruses, especially influenza viruses. Favipiravir has also been used to treat patients with mild to moderate COVID-19 disease. However, various side effects, including neurological side effects, have been reported related to the use of favipiravir. Therefore, in this study, we aimed to investigate the possible effects of favipiravir alone or in combination with vitamin C on aged rats' brain tissue and the possible mechanisms of these effects. A total of 30 rats used in the study were randomly divided into 5 equal groups and the first group was kept as the control group. High-dose (100 mg/kg) or low-dose (20 mg/kg) favipiravir was administered alone or in combination with vitamin C (150 mg/kg) to other groups. Administration of both high and low doses of favipiravir significantly increased TBARS levels in brain tissue of aged rats. Similarly, both high and low doses of favipiravir led to significant increases in Bcl-2 and caspase-3 relative mRNA expression. However, only low dose favipiravir caused a significant increase in iNOS and IL-1 & beta; relative mRNA expression levels. Similar results were also observed in histopathological examinations. However, co-administration of vitamin C with favipiravir attenuated some of the adverse effects of favipiravir. In conclusion, in this study, it was shown that the use of favipiravir caused some adverse effects through oxidative, inflammatory and apoptotic processes in the brain tissue of aged rats, and the potential of vitamin C to alleviate these effects.