Background: Doxorubicin (DOX) is a broad-spectrum chemotherapeutic drug widely used in the treatment of a variety of cancers. Although doxorubicin is considered a very efficient chemotherapeutic drug, it also kills healthy cells, especially those under rapid and constant proliferation, such as the male germ cells and lead to infertility. It acts by generating reactive oxygen species in target cells. This study was carried out to investigate the effects of pentoxifylline, with antioxidant and anti-inflammatory activities, against sperm parameters changes due to DOX treatment in mice. Methods: Twenty-four male NMRI (Naval Medical Research Institute) mice were assigned randomly into four groups (n = 6): control, Doxorubicin (Dox, 2mg/kg/weekly), Pentoxifylline (PTX, 100mg/kg/daily) and PTX+Dox. After 35 days intraperitoneal tretment, Sperm samples were collected from cauda epididymidis and used to assess count, motility, viability, morphology, tail length, DNA damage (using acridine orange and aniline blue staining techniques) and daily sperm production. The results were analyzed by one-way ANOVA and Tukey's test. Results: Dox caused significant decrease in sperm count, motility, viability, morphology, tail length and daily sperm production along with elevated sperm abnormality in comparing to the control group (p<0.001). These negative effects were ameliorated following the intervention with PTX. There was no significant difference in sperm DNA damage in Dox treatment groups compared to the control group. Conclusion: Our results suggest that pentoxifylline with its antioxidant properties, can reduce the toxic effects of doxorubicin and improve sperm parameters.
