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Abstract Chemotherapy may result in temporary or permanent gonadal toxicity in male patients. Loss of fertility potential can be devastating to patients, especially, during the child-bearing period. The present study was planned to investigate the possible protective effect of melatonin, in a rat model of cisplatin-induced testicular toxicity. Forty five adult male albino rats were divided into four groups; group I Control (n=15) received 0.9% sodium chloride and/or distilled water as a vehicle. group II (n=10) were injected intraperitoneally (I.P.) with a single dose 7 mg/kg of cisplatin & were sacrificed after 10 days. group III (n=10) received melatonin daily orally at a dose of 8 mg/kg/day for 10 days. group IV (n=10); oral melatonin administration started 5 days before the single I.P. injection of cisplatin, followed by continuation of melatonin for further 10 days. Testicular sections were subjected to H&E, immunohistochemical staining for anti-inducible nitric oxide synthase (iNOS) and anti-androgen receptor (AR). The study proved the protective effect of melatonin against testicular toxicity, when administered prior to and concomitant with cisplatin therapy; confirming the anti-oxidant potential of melatonin |