Abstract
Mercury is a highly toxic heavy metal with definite cardiotoxic properties and can affect the health of humans and animals through diet. Selenium (Se) is a heart-healthy trace element and dietary Se has the potential to attenuate heavy metal-induced myocardial damage in humans and animals. This study was designed to explore antagonistic effect of Se on the cardiotoxicity of mercuric chloride (HgCl2) in chickens. Hyline brown hens received a normal diet, a diet containing 250 mg/L HgCl2, or a diet containing 250 mg/L HgCl2 and 10 mg/kg Na2SeO3 for 7 weeks, respectively. Histopathological observations demonstrated that Se attenuated HgCl2-induced myocardial injury, which was further confirmed by the results of serum creatine kinase and lactate dehydrogenase levels assay and myocardial tissues oxidative stress indexes assessment. The results showed that Se prevented HgCl2-induced cytoplasmic calcium ion (Ca2+) overload and endoplasmic reticulum (ER) Ca2+ depletion mediated by Ca2+-regulatory dysfunction of ER. Importantly, ER Ca2+ depletion led to unfolded protein response and endoplasmic reticulum stress (ERS), resulting in apoptosis of cardiomyocytes via PERK/ATF4/CHOP pathway. In addition, heat shock protein expression was activated by HgCl2 through these stress responses, which was reversed by Se. Moreover, Se supplementation partially eliminated the effects of HgCl2 on the expression of several ER-settled selenoproteins, including selenoprotein K (SELENOK), SELENOM, SELENON, and SELENOS. In conclusion, these results suggested that Se alleviated ER Ca2+ depletion and oxidative stress-induced ERS-dependent apoptosis in chicken myocardium after HgCl2 exposure.
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This work was supported by the National Natural Science Foundation of China (grant number 32273088), the Youth Innovation and Technology Program in Colleges and Universities of Shandong Province (grant number 2020KJF009), and Funds of Shandong “Double Tops” Program, and Funds of Shandong “Double Tops” Program.
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Rui-Feng Fan and Pei-Chao Gao contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Pei-Chao Gao, An-Qi Wang, Xue-Wei Chen, Han Cui, and Yue Li. The first draft of the manuscript was written by Pei-Chao Gao and An-Qi Wang, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Gao, PC., Wang, AQ., Chen, XW. et al. Selenium alleviates endoplasmic reticulum calcium depletion-induced endoplasmic reticulum stress and apoptosis in chicken myocardium after mercuric chloride exposure. Environ Sci Pollut Res 30, 51531–51541 (2023). https://doi.org/10.1007/s11356-023-25970-1
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DOI: https://doi.org/10.1007/s11356-023-25970-1