en Pharmacokinetics/Dynamics Pharmacokinetics/Dynamics Experimental research article Experimental research article <p dir="ltr" style="text-align: justify;"><span style="font-size: 11px;">Introduction: <font face="Arial,Arial"><font face="Arial,Arial">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. </font></font></span><span style="font-size: 11px;">Materials and Methods: <font face="Arial,Arial"><font face="Arial,Arial">Forty adult NMRI mice (30 &plusmn; 5 g) were divided into two groups. Control and busulfan treated group were administered with 100 &muL 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. </font></font></span><span style="font-size: 11px;">Results: <font face="Arial,Arial"><font face="Arial,Arial">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). </font></font></span><span style="font-size: 11px;">Conclusion: <font face="Arial,Arial"><font face="Arial,Arial">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.</font></font></span></p> Apoptosis, Bcl-2 family genes, Busulfan, Epididymal sperm, Oxidative stress. 208 215 http://ppj.phypha.ir/browse.php?a_code=A-10-878-1&slc_lang=en&sid=1 Parva Nasimi parvanasimi62@yahoo.com 3200319475328460015858 3200319475328460015858 No Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran Mohammad Reza Tabandeh m.tabandeh@scu.ac.ir 3200319475328460015859 3200319475328460015859 No Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran Akbar Vahdati avahdatim@yahoo.com 3200319475328460015860 3200319475328460015860 Yes Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran Saeed Khatamsaz Saeed1617@yahoo.com 3200319475328460015861 3200319475328460015861 No Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran