| Summary: | This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr<sup>6+</sup>)-induced toxicity. Potassium dichromate (K<sub>2</sub>Cr<sub>2</sub>O<sub>7</sub>) and selenium-enriched yeast (SeY) were used to construct the single Cr<sup>6+</sup> and combined Se/Cr<sup>6+</sup> exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr<sup>6+</sup> group, and Cr<sup>6+ </sup>group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr<sup>6+</sup> were evaluated using histopathological assessment, serum biochemical tests, oxidative stress kits, ELISA, qPCR, and Western blotting. On the whole, there were no significant changes between the C and Se groups. The spleen organ index in the Cr<sup>6+</sup> group was significantly decreased, but SeY increased spleen organ index to a certain extent. The levels of SOD and GSH were reduced, and the MDA content was elevated by Cr<sup>6+</sup>; however, these changes were mitigated by Se/Cr<sup>6+</sup> exposure. Importantly, Cr<sup>6+</sup> exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Cr<sup>6+</sup>group. Furthermore, Cr<sup>6+</sup> significantly decreased the levels of T-globulin, IgA, IgM, and IgG in serum. Contrarily, dramatically more T-globulin IgA, IgM, and IgG were found in the Se/Cr<sup>6+</sup>group than in the Cr<sup>6+</sup> group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr<sup>6+</sup> groups, while they were downregulated in Se/Cr<sup>6+</sup> group compared to that in Cr<sup>6+</sup> group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr<sup>6+</sup> exposure, but the SeY supplement relived the expression levels mediated by Cr<sup>6+</sup> exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr<sup>6+</sup>, and we speculate that the NF-κB signaling pathway is one of its mechanisms.
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