Combined apocynin and carvedilol protect against cadmium-induced testicular damage via modulation of inflammatory response and redox-sensitive pathways

Testicular damage is considered a severe complication of cadmium (Cd) exposure which is associated with tissue oxidative stress damage, inflammation, and apoptosis. The present study investigated the antioxidant, anti-inflammatory, and anti-apoptotic activities of apocynin (APO) and carvedilol (CVD) against Cd-induced acute testicular damage. Rats were allocated into five groups as follows: normal control (received vehicle), Cd control group (2 mg/kg, i.p), APO-treated group (25 mg/kg, P.O.), CVD-treated group (10 mg/kg, P.O.), and combination group (APO + CVD). Blood, serum, and tissue samples were withdrawn for hematological, biochemical, molecular, and histological analyses. The present results confirmed testicular damage after cd exposure as indicated by alteration of serum hormonal levels, hematological defects, histopathological changes, and loss of steroidogenic functions. Besides, Cd injection-induced up-regulation of NADPH oxidase, MDA, NF-kappa B, IRF3, MPO, pro-inflammatory cytokines, Bax, and cleaved caspase-3 expression concomitant with down-regulation of Nrf2, GSH, SOD, and Bcl2 expression. Interestingly, pretreatment with APO and/or CVD significantly relieved Cd-induced testicular damage at cellular and molecular levels. Notably, the combined protective effect of APO plus CVD was higher than the protective effect of each drug alone. Overall, combined APO and CVD could serve as a good candidate for protection against Cd-induced testicular damage via suppression of inflammatory response and modulation of the redox-sensitive pathway.