busulfan induces oxidative stress- and bcl-2 family gene-related apoptosis in epididymal sperm and testis of adult male mice

Introduction: busulfan as a chemotherapeutic agent causes testicular germinal epithelium depletion and cytotoxicity in germ cells. the aim of this study was to assess antioxidant status, reactive oxygen species (ros) generation and apoptosis-related genetic markers of adult male mouse sperm following busulfan treatment.materials and methods: forty adult nmri mice (30 ± 5 g) were divided into two groups. control and busulfan treated group were administered with 100 µl dimethyl sulfoxide and 3.2 mg/kg/day busulfan for 4 days, respectively. the superoxide dismutase and glutathione peroxidase assays were used for analyzing antioxidant status. then, the levels of bcl-2 family gene expression, lipid peroxidation and cytotoxicity were evaluated by real-time pcr, thiobarbituric and lactate dehydrogenase assays, respectively.results: the results showed significant decrease on antioxidant status, increase on lipid peroxidation and lactate dehydrogenase in epididymal sperm and testis of busulfan treated mice in comparison with control (p < 0.05). real time pcr demonstrated significantly increased-bax gene expression and decreased-bcl-2 gene expression in epididymal sperm of treated group (p < 0.05).conclusion: the high levels of lipid peroxidation and lactate dehydrogenase revealed increased-ros and severe cytotoxicity in epididymal sperm and testis tissue following busulfan treatment at clinical dose. the oxidative stress and increased-ros may induce bcl-2 family gene expression-related apoptosis following busulfan therapy in normal cells.