Selenium regulates the mitogen-activated protein kinase pathway to protect broilers from hexavalent chromium-induced kidney dysfunction and apoptosis.

Hexavalent chromium [Cr (VI)] is a common environmental pollutant. Although selenium (Se) can antagonize the toxicity of Cr (VI), the specific underlying mechanism has not been identified. To investigate this mechanism, we used potassium dichromate (K2Cr2O7) and selenium-rich yeast (SeY) to construct single Cr (VI)- and combined Se/Cr (VI)-exposed broiler models during a 42-day period. Broilers were randomly assigned to the control (C), SeY (Se), SeY + Cr (VI) (Se/Cr), and Cr (VI) (Cr) groups. The antagonistic mechanisms of Se and Cr (VI) were evaluated using histopathological evaluation, serum and tissue biochemical tests, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The results suggested that Se alleviated the morphological and structural damage to renal tubules and glomeruli, while reducing the organ index, creatinine levels, and blood urea nitrogen levels in the kidneys of Cr (VI)-exposed broilers. Furthermore, Cr (VI) reduced the levels of superoxide dismutase and glutathione, and increased the levels of malondialdehyde, in broiler kidney tissues. However, Se alleviated Cr (VI)-induced oxidative stress by increasing the levels of superoxide dismutase and glutathione, and decreasing the levels of malondialdehyde, within a certain range. Compared to the C group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly increased, whereas those of ERK, p-ERK, and p-ERK/ERK decreased, in the Cr group. Compared to the Cr group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly decreased, whereas those of ERK, p-ERK, and p-ERK/ERK increased, in the Se/Cr group. Furthermore, the levels of p53, c-Myc, Bax, Cyt-c, caspase-9, and caspase-3 significantly increased, and those of Bcl-2 and Bcl-2/Bax significantly decreased, following Cr (VI) exposure, while Se restored the expression of these genes. In conclusion, our findings suggest that SeY can protect against Cr (VI)-induced dysfunction and apoptosis by regulating the mitogen-activated protein kinase pathway activated by oxidative stress in broiler kidney tissues.

Selenium-Enriched Yeast Relieves Hexavalent Chromium Toxicity by Inhibiting NF-κB Signaling Pathway in Broiler Spleens.

This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr6+)-induced toxicity. Potassium dichromate (K2Cr2O7) and selenium-enriched yeast (SeY) were used to construct the single Cr6+ and combined Se/Cr6+ exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr6+ group, and Cr6+ group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr6+ 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 Cr6+ 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 Cr6+; however, these changes were mitigated by Se/Cr6+ exposure. Importantly, Cr6+ exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Cr6+group. Furthermore, Cr6+ 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/Cr6+group than in the Cr6+ group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr6+ groups, while they were downregulated in Se/Cr6+ group compared to that in Cr6+ group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr6+ exposure, but the SeY supplement relived the expression levels mediated by Cr6+ exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr6+, and we speculate that the NF-κB signaling pathway is one of its mechanisms.

Selenium Alleviates Chromium(VI)-Induced Ileum Damage and Cecal Microbial Disturbances in Mice.

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants caused by its broad industrial applications. Importantly, exposure to Cr(VI) induces oxidative damage and apoptosis in animal cells. Studies have shown that selenium (Se) can alleviate the toxic effects of Cr(VI) by functioning as an antioxidant and/or by chelating Cr(VI) into biologically inert complexes, but the underlying mechanism remains unknown. Here, we evaluated whether Se can ameliorate ileum damage and cecal microbial disturbances induced by Cr(VI) in vivo. Mice administered Cr(VI) for 30 days presented histopathological damage, reduced responses to oxidative stress, and increased expression of apoptosis-related genes in the ileum compared with those in the control (non-exposed) group. Se alleviated the histopathological damage and decreased the oxidative stress and apoptosis induced by Cr(VI) in the ileum. In addition, Cr(VI) disturbed cecal microflora, and it was partially reversed by Se treatment. These findings demonstrate that the damaging and potentially pathological effects of Cr(VI) on the ileum and cecal microflora can be effectively alleviated with Se treatment.