Subacute Cadmium Exposure Induces Necroptosis in Swine Lung via Influencing Th1/Th2 Balance.

Cadmium (Cd) is a type of toxic substance, which widely exists in nature. However, the effect of Cd exposure on the toxicity of swine lungs and its underlying mechanism involved have not yet been reported. In our study, we divided swine into two groups, including a control group (C group) and Cd-exposed group. Swine in the C group were fed a basic diet, whereas swine in the Cd group were fed a 20 mg Cd/kg diet. Immunofluorescence, qRT-PCR, western blot analysis, and H&E staining were performed to detect necroptosis-related indicators. Our results found that after Cd exposure, Th1/Th2 imbalance occurred, miR-181-5p was down-regulated, TNF-α expression was increased, and the NF-κB/NLRP3 and JAK/STAT pathways and RIPK1/RIPK3/MLKL axis were activated. Furthermore, histopathological examination showed necrosis in swine lung after Cd exposure. Together, the above-mentioned results indicate that subacute Cd exposure is closely linked with necroptosis in swine lung. Our study provided evidence that Cd may act through miR-181-5p/TNF-α to induce necroptosis in swine lung. The findings of this study supplement the toxicological study of Cd and provide a reference for comparative medicine.