Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats

Objective: To evaluate the effect of melatonin on cyclophosphamide (CP)- and cisplatin-induced testicular toxicity with use of sperm parameters and biochemical and histopathologic approaches. Design: Experimental study. Setting: Vakif Gureba Hospital, Istanbul, Turkey. Animals: Six-week-old adult male Wistar albino rats (N = 48). Intervention(s): Cyclophosphamide was administered to rats by gavage at a single dose of 100 mg/kg body weight, only once. Cisplatin was injected intraperitoneally at single doses of 7 mg/kg/d for five consecutive days. Melatonin was both administered separately and coadministered with CP and cisplatin intraperitoneally at a dose of 10 mg/kg body weight. Main Outcome Measure(s): Body and testicular weight, epididymal sperm characteristics, plasma T, and histopathologic structure of the testicular tissue were determined. Malondialdehyde (MDA) and reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. Result(s): Body and testicular weight, epididymal sperm count, motility and morphology, plasma T levels, the activities of GSH-Px, and GSH levels were significantly decreased whereas the level of MDA was significantly increased in rats of the CP and cisplatin group. Melatonin treatment increased GSH levels and GSH-Px activity, decreased MDA level in testicular tissue, and increased plasma T level. Cyclophosphamide and cisplatin caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant maturation arrest, and perivascular fibrosis. Melatonin significantly improved histopathologic changes. Conclusion(s): Melatonin may prevent CP- and cisplatin-induced testicular damage. (Fertil Steril (R) 2009;92:1124-32. (C)2009 by American Society for Reproductive Medicine.)