Cyclophosphamide (CP) is one of the chemotherapeutic drugs, which plays its role by interfering with all rapidly proliferating tissues like cancer and testis. The aim of this study was to investigate the protective effect of pentoxifylline (PTX) on the sperm parameters, spermatogenesis indices, biochemical alterations and gene expressions, in adult male mice treated with CP. A total of 24 male NMRI mice were divided into four groups: control, CP group (15 mg/kg weekly), PTX (100 mg/kg daily) and CP + PTX and treated for 35 days with the intraperitoneal injection. A significant decrease in the spermatogenesis indices, Leydig cells, sperm motility, viability, count, tail length and daily sperm production was found in the CP group compared to the control group. The results of this study indicate that PTX prevented these adverse effects of CP and decreased the number of apoptotic cells. Moreover, the CP group showed decreased levels of total antioxidant capacity, testosterone, lipid peroxidation and the expression of cytochrome P450 and 3β-hydroxysteroid, all of which were neutralized in the CP + PTX group. It seems that PTX has the potential to be used in therapeutic regimens of cancer patients to reduce the side effects of CP. However, more research is needed to evaluate this prevention in mice models of cancer.
