Captopril and telmisartan ameliorate cisplatin-induced testicular damage in rats via anti-inflammatory and antioxidant pathways

Despite the prevalent clinical applications of cisplatin, serious toxic side effects comprising reproductive toxicity confine its therapeutic efficacy. Thus, the current study explored the possible protective effect of captopril and telmisartan against cisplatin-induced testicular damage in rats. Captopril (100 mg/kg) and telmisartan (10 mg/kg) were orally administered for 15 days, whereas cisplatin (10 mg/kg; i.p.) was injected as a single dose at the 12 day to induce testicular damage in adult male Sprague-Dawley rats. Cisplatin prominently decreased reproductive organs weights, sperm count, sperm motility, and increased sperm abnormalities, along with histopathological damage of testicular tissues. In addition, it resulted in a significant decline in serum testosterone as well as testicular enzymatic and non-enzymatic antioxidants levels (superoxide dismutase, catalase, glutathione peroxides, and reduced glutathione), parallel to a remarkable elevation in testicular content of malondialdehyde, nitric oxide, tumor necrosis factor-α, and nuclear factor-kappa B. Treatment with captopril or telmisartan markedly attenuated cisplatin-induced injury by suppression of oxidative/nitrosative stress and inflammation, amendment of antioxidant defenses, as well as improvement of steroidogenesis, spermatogenesis and testicular histological features. This study suggests a novel therapeutic application for captopril and telmisartan as protective agents against cisplatin-induced testicular toxicity through their promising anti-inflammatory and antioxidant capacities.