Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm

Treatment with cyclophosphamide (CP), a commonly used anticancer and immunosuppressive agent, may result in oligospermia and azoospermia. CP administration induces oxidative stress and is cytotoxic to normal cells. In this context, we have studied the effect of an established antioxidant, lipoic acid on its influence on CP-induced oxidative injury in rat sperm. In this study, we have assessed the possible protective efficacy of lipoic acid on the sperm characteristics, peroxidative damages and abnormal antioxidant levels in the epididymal sperm of CP-administered rats. Male Wistar rats of 140+/-20 g were categorized into four groups. Two groups of rats were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to CP administration). A vehicle treated control group and a lipoic acid drug control group were also included. CP-treated rats showed a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. The epididymal sperm of untreated CP-exposed rats showed 1.9-fold increase in lipid peroxidation, along with a significant increase in protein carbonyl level. These changes were associated with significant increase in DNA damage in the sperm as evidenced by increased single strand breaks in fluorimetric analysis of DNA unwinding (FADU). In rats treated with CP, abnormal changes in the activities/levels of enzymic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants, were also observed. Pretreatment with lipoic acid improved the semen quality and reduced the oxidative stress and DNA damage induced by CP, thereby demonstrating the protection rendered by lipoic acid.