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-α) and nuclear factor-kappa B (NF-κB). 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.