Journal
JOURNAL OF ADVANCED RESEARCH
Volume 35, Issue -, Pages 129-140Publisher
ELSEVIER
DOI: 10.1016/j.jare.2021.04.002
Keywords
Cr(VI); Deacetylation; Sirt1; Oxidative stress; Apoptosis; Liver injury
Categories
Funding
- National Natural Science Foundation of China [31972754]
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This study demonstrates that Cr(VI) induces liver injury in rats by inhibiting the deacetylation of Sirt1, leading to inflammatory response and apoptosis in hepatocytes. When administered Res as an activator of Sirt1, the deacetylation of Sirt1 is enhanced, resulting in alleviation of inflammatory response and apoptosis.
Introduction: Hexavalent chromium (Cr(VI)), one of the toxic heavy metals, poses a serious threat to human and animal health. Protein acetylation regulates the structure and function of most proteins in a variety of ways. However, the hepatotoxicity of Cr(VI) and whether it is related to deacetylation remains largely unknown. Objectives: We aimed to explore the link between the deacetylation of silent information regulator two ortholog 1 (Sirt1) and hepatotoxicity induced by Cr(VI) exposure, and to better clarify the biological mechanism of liver injury induced by Cr(VI). Methods: We established a model of liver injury of K2Cr2O7 by injecting rats intraperitoneally for 35 days continuously and adding resveratrol (Res) to further explore the link between deacetylation and hepatotoxicity. Results: The results revealed that Cr(VI) induced inflammatory response and apoptosis in hepatocytes. Furthermore, Cr(VI) reduced Sirt1 expression and inhibited the deacetylation of Sirt1 to downstream key transcription factors, including nuclear factor erythroid 2-related factor 2 (Nrf2), Forkhead box O3 (FOXO3), and nuclear factor-kappa B (NF-kappa B). Conversely, when Res was administered as an activator of Sirt1, the deacetylation of Sirt1 was enhanced, and inflammatory response and apoptosis were significantly alleviated. Conclusion: In summary, this work firstly demonstrates that Cr(VI) induces liver injury in rat by inhibiting the deacetylation of Sirt1, which is of positive significance for protecting the natural environment and animal health from chronic Cr poisoning. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.
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