Evaluating the Potential Adverse Effects of Favipiravir on Biochemical, Histopathological, and Spermatological Parameters in Male Rats' Testicular Tissue

Abstract

Favipiravir is a selective RNA polymerase inhibitor and a broad-spectrum antiviral drug. Favipiravir reduces cell proliferation by inhibiting RNA transcription, particularly in rapidly proliferating cells such as spermatogonia. The aim of this study was to investigate the effects and mechanism of action of favipiravir (T-705) on sperm quality and testicular tissue in rats. A total of 60 Sprague-Dawley rats, 30 in each group, were used in our study. Rats were randomly divided into two groups, control and experimental. Rats were killed on Day 14, Day 21, and Day 50 to observe short- and long-term effects. Oxidative stress, apoptosis, proliferation, aromatase activity, inflammation, histopathological changes, and epididymal sperm quality were examined in the testicular tissue of rats. Favipiravir administration decreased SOD activity and GSH levels and increased MDA levels and 8-OHdG levels in the testes of rats. It increased the levels of Caspase-3 and NF-ĸB, which are apoptotic markers, and decreased the levels of NRF2, PI3K, and Bcl-2, which play a role in the regulation of apoptosis. Favipiravir led to disruption of the seminiferous tubules and disturbances in the structure of cells in the testis. In spermatological analysis, total motility value and epididymal spermatozoa density decreased. On Day 50, the favipiravir groups had higher rates of abnormal spermatozoa, DNA damage, and acrosome damage. In conclusion, favipiravir administration induced oxidative stress by increasing MDA levels and decreasing SOD activity and GSH levels in the testicular tissue of rats. It also affects the release of reproductive hormones by altering the hypothalamic-pituitary axis. Favipiravir administration decreases the expression of genes that induce sperm capacitation and acrosome reaction and decreases sperm quality by causing changes in testicular histoarchitecture. Study results reveal that favipiravir treatment negatively affects testes and semen quality.