Evaluation of Nephrotoxic Properties of Favipiravir Using the RPTEC cell model

Abstract

Scientific relevance. Favipiravir is an antiviral RNA polymerase inhibitor used to treat COVID-19. An adverse drug reaction associated with the use of favipiravir is renal disorder.Aim. This study aimed to investigate favipiravir nephrotoxicity by assessing its effects on the integrity of a monolayer formed by renal proximal tubular epithelial cells (RPTECs).Materials and methods. This study focused on an RPTEC monolayer culture that was seeded at a density of 6×104 cells/cm2 on plates with membrane inserts with 0.4 μm pores. Favipiravir was added to the plate wells at a concentration of 5, 10, or 15 μg/mL. The nephrotoxicity evaluation relied on measuring the transepithelial electrical resistance (TEER) of the RPTEC monolayer. A TEER value of 120–140 Ω×cm2 was considered an indication of nephrotoxicity.Results. RPTEC incubation with favipiravir led to a dose-dependent decrease in the TEER values. However, the TEER values after 6 days of incubation ranged within 250–280 Ω×cm2 and were above the critical thresholdof 120–140 Ω×cm2.Conclusions. The results of this study indicate that favipiravir has no pronounced effect on the TEER of the RPTEC monolayer.

Keywords

• favipiravir
• nephroctoxicity
• rptec
• cell lines
• transepithelial electrical resistance
• non-clinical studies
• in vitro