Cisplatin, a common chemotherapeutic drug, can induce testicular toxicity. Methylene blue, a potent antioxidant, can inhibit the generation of free radicals. This research aimed to study the protective effect of methylene blue against the cisplatin-induced toxicity of the reproductive system in rats. 35 male Wistar rats were divided into five groups: the control group, the cisplatin group (a single dose of 5 mg/kg cisplatin), the low-dose and high-dose methylene blue + cisplatin (2 and 4 mg/kg of methylene blue, respectively, for 7 days) and the methylene blue group (4 mg/kg of methylene blue, for 7 days). The treatments were applied through intraperitoneal injection. Cisplatin treatment reduced the sperm parameters and serum testosterone levels significantly. Methylene blue treatment increased the sperm count (p < .001), viability (p < .001) and motility (p < .001) compared to the cisplatin group. The methylene blue group showed a significant increase in the levels of testosterone compared to the cisplatin group (p < .001) and reverted histopathological changes in cisplatin-treated groups. Immunohistochemical evaluation of the caspase-3 protein revealed that the treatment with methylene blue has significant anti-apoptotic effects on testicular tissue damage. In conclusion, methylene blue can attenuate the cisplatin-induced histological damages and improve the sperm parameters.
