Naringenin palliates cisplatin and doxorubicin gonadal toxicity in male rats

Cisplatin (CP) and doxorubicin (DX) can cause testicular injury by inducing oxidative/nitrosative stress, inflammation, and apoptosis, Naringenin (NG) has antioxidant, antinitrative, anti-inflammatory, and anti-apoptotic effects. This study investigated the potential ability of NG to block gonadotoxicity induced CP and DX in male rats. The rats received one injection of either CP (10 mg/kg, i.p.) or DX (15 mg/kg, i.p.), and treated with NG (50 mg/kg/day, p.o.) for 10 days beginning 6 days prior to CP and DX administration. NG significantly prevented the decreases of serum testosterone and inhibin B in rats received CP and DX. Additionally, NG significantly decreased the elevated testicular malondialdehyde, tumor necrosis factor-alpha/interleukin-10 ratio, and caspase-3 in CP- and DX-treated rats. NG also significantly raised the decreased testicular Bcl-2/Bax ratio, and total antioxidant status in CP- and DX-challenged rats. In addition, NG significantly increased P-glycoprotein level in testes of rats received CP and DX. Moreover, NG significantly decreased the testicular histopathological injury, and immunohistochemical expression of inducible nitric oxide synthase induced by CP and DX in rat testes. It was concluded that NG impeded gonadotoxicity of CP and DX in male rats by mitigating oxidative stress, nitrosative stress, inflammation, and apoptosis.