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Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function

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Abstract

Sodium butyrate (NaBu) is a by-product of microbial fermentation of dietary fiber in the gastrointestinal tract and has been shown to increase the activity of antioxidant enzymes, such as catalase or heme oxidase-1, in vivo. However, the mechanism of this effect is still unclear. This study investigated the antioxidant effect of NaBu on HepG2 cells under H2O2-induced oxidative stress. NaBu (0.3 mM) attenuated cell death and accumulation of reactive oxygen species and improved multiple antioxidant parameters in H2O2-injured HepG2 cells. NaBu inhibited glycogen synthase kinase-3 beta (GSK-3β) by increasing the p-GSK-3β (Ser9) level and promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increased the expression of downstream antioxidant enzymes. Together with promotion of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial DNA copy number, NaBu modulated energy metabolism and mitochondrial function, decreasing glycolysis, increasing β-oxidation, and enhancing the tricarboxylic acid cycle and oxidative phosphorylation. NaBu increased mitochondrial manganese-superoxide dismutase and glutathione peroxidase activity. In conclusion, NaBu protected HepG2 cells against oxidative stress by modulating Nrf2 pathway activity and mitochondrial function.

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Change history

  • 05 October 2017

    Volume 73 issue 3 was published with an incorrect cover date. Correct is August 2017. The Publisher apologizes for this mistake and all related inconveniences caused by this.

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Acknowledgments

The study was supported by the 12th Five-year Plan for Science and Technology Development of China (No. 2012BAD33B05).

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Authors and Affiliations

  1. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China

    Xingan Xing, Xue Tang & Guowei Le

  2. School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China

    Xingan Xing, Xue Tang, Panpan Wang, Yingrui Li, Yongjuan Sun & Guowei Le

  3. Wuxi No.1 Senior High School, Wuxi, Jiangsu, China

    Zheshu Jiang

  4. Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, Jiangsu, China

    Sixiang Zou

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  1. Xingan Xing
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  2. Zheshu Jiang
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Correspondence to Xue Tang.

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An erratum to this article is available at https://doi.org/10.1007/s13105-017-0593-x.

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Xing, X., Jiang, Z., Tang, X. et al. Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function. J Physiol Biochem 73, 405–414 (2016). https://doi.org/10.1007/s13105-017-0568-y

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  • DOI: https://doi.org/10.1007/s13105-017-0568-y

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