Etanercept Mitigates Cadmium Chloride-induced Testicular Damage in Rats "An Insight into Autophagy, Apoptosis, Oxidative Stress and Inflammation"

Rationale Cadmium (Cd) is an environmental and occupational toxin that represents a serious health hazard to humans and other animals. One of the negative consequences of cadmium exposure is testicular injury. Objective This study aimed to investigate the therapeutic effect of etanercept against cadmium chloride-induced testicular damage and the probable underlying mechanisms of its action. Methods A total of sixty rats were divided into six groups: control, cadmium chloride (CdCl2) (7 mg/kg i.p.), and CdCl2 treated with etanercept (5,10 and 15 mg/kg s.c.) and etanercept only (15 mg/kg s.c.). CdCl2 was administrated as a single dose, while etanercept was administered every 3 days for 3 weeks. Results CdCl2 reduced serum testosterone, testicular glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). However, it elevated the levels of malondialdehyde (MDA) and microtubule-associated protein light chain 3B (LC3B) in the testes. Cadmium caused pathogenic alterations as well as increased levels of inflammatory biomarkers such as tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappa B (NF-kappa B). Besides, the gene expressions of caspase-3 and inducible nitric oxide synthase (i-NOS) and Beclin-1 protein increased with CdCl2 exposure. Interestingly, etanercept relieved the previous toxic effects induced by CdCl2 in a dose-dependent manner as evidenced by inhibition of oxidative stress, inflammatory markers, Beclin-1, LC3B, and caspase-3 accompanied by improvement in histopathological changes. Conclusion Etanercept provides a potential therapeutic approach to treat testicular tissue against the damaging effects of Cd by reducing oxidative stress, inflammation, apoptosis, and autophagy.