Background: Doxorubicin is a widely used chemotherapeutic agent causing testicular toxicity and might lead to male infertility. The present study aims to investigate the protective effects of pentoxifylline as a potent antioxidant on doxorubicin-induced testicular injury. Methods: 24 adult male Naval Medical Research Institute (NMRI) mice were randomly divided into four groups: Control, Doxorubicin (Dox, 2mg/kg/weekly), Pentoxifylline (PTX, 100mg/kg/daily) and PTX+Dox. After 35 days’ intraperitoneal treatment, the left testis was removed and after fixation, tissue processing and staining by hematoxylin-eosin (H&E) method, was examined by stereology technique. The serum concentration of testosterone hormone, malondialdehyde (MDA) and the total antioxidant capacity (TAC) were assessed. The results were analyzed using one-way ANOVA and Tukey's test. Results: The results showed a significant decrease in body and testicular weight, total volume of testes, volume and length of seminiferous tubules and also diameter and height of the germinal epithelium, the number of germ cells, spermatogenesis indexes and testosterone and TAC level in the doxorubicin treatment group compared to the control group (p<0.001). Significant increase was observed in the volume of interstitial tissue and MDA level in the DOX group compared to the control group (p<0.001). In co-treatment group, pentoxifylline significantly reduced the toxic effects of doxorubicin and improved the above parameters compared to the doxorubicin group. Conclusion: The results showed that pentoxifylline as an antioxidant is beneficial in reducing the toxic effects of DOX in testis by enhancing antioxidant activity and decreasing MDA and oxidative stress.
