Mechanism of protection by diallyl disulfide against cyclophosphamide-induced spermatotoxicity and oxidative stress in rats

The present study investigated the protective effects and the mechanism of action of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced spermatotoxicity and oxidative damage in rats. DADS (50 mg/kg/day) was administered orally to rats once daily for 10 days. On the first 2 days, CP (150 mg/kg/day) was injected intraperitoneally to rats 1 h after DADS treatment. CP caused decreases in body weight, food consumption, epididymal sperm motility, and the number of spermatogenic germ cells and increases in the testes and epididymides weights, spermatogenic cell apoptosis, and histopathologic alterations in the testis. The significant decreases in glutathione content and catalase, glutathione S-transferase, and glutathione reductase activities and the significant increase in malondialdehyde content indicated that CP-induced testicular toxicity was mediated through oxidative stress. In contrast, DADS administration significantly attenuated the spermatotoxicity of CP, including attenuating the decreases in sperm motility and the number of spermatogenic germ cells and the increases in reproductive organ weights, oxidative stress, apoptotic changes, and histopathologic alterations. DADS also significantly increased CYP2B1/2 and CYP3A1 expression and significantly decreased CYP2C11 expression. The results show that the protective effects of DADS against CP-induced spermatotoxicity may be mediated by its ability to decrease metabolic activation of CP by inhibiting CYP2C11 and inducing CYP3A1, and by its potent antioxidant and antiapoptotic effects.