Background: 5-Fluorouracil (5-FU) is one of the anti-metabolite drugs which, in addition to its chemotherapy properties, may also disturb the cell metabolism and the survival of normal cells, which is the basis of developmental and reproductive toxicities. This study was conducted in order to investigate the antioxidant effect of folic acid on testis structure and spermatogenesis process of mice treated with 5-fluorouracil. Materials and Methods: 24 adult male NMRI mice were divided into 4 groups (n=6), control 5-fluorouracil (15 mg/kg, 5 consecutive days), folic acid (1 mg/kg, daily) and 5-fluorouracil + folic acid. After 35 days of treatment, testicular tissue parameters by stereological methods and testosterone levels were estimated. The data were analyzed by One-Way ANOVA and Tukey's test and considered significant at the level of (P<0.05). Results: A significant decrease in the weight and volume of the testis, the volume, diameter and height of the germinal epithelium of the seminiferous tubules and the level of testosterone hormone and a significant increase in the volume of the interstitial tissue were observed in the 5-fluorouracil group compared to the control group (P<0.01). The number of germ cells and spermatogenesis indices in the group treated with 5-fluorouracil showed a significant decrease compared to the control group (P<0.001). In the simultaneous treatment group, folic acid partially reversed these parameters and made them close to the control group. Conclusion: Folic acid as an antioxidant can improve tissue damage caused by 5-fluorouracil and prevent testicular tissue destruction by inhibiting free radicals.
