Xing Xingan, Jiang Zheshu, Tang Xue, Wang Panpan, Li Yingrui, Sun Yongjuan, Le Guowei, Zou Sixiang
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
J Physiol Biochem. 2016 Aug;73(3):405-414. doi: 10.1007/s13105-017-0568-y. Epub 2017 Jun 10.
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 HO-induced oxidative stress. NaBu (0.3 mM) attenuated cell death and accumulation of reactive oxygen species and improved multiple antioxidant parameters in HO-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.
丁酸钠（NaBu）是膳食纤维在胃肠道中微生物发酵的副产物，且已证实在体内可提高抗氧化酶（如过氧化氢酶或血红素氧化酶-1）的活性。然而，这种作用的机制仍不清楚。本研究调查了NaBu在HO诱导的氧化应激下对HepG2细胞的抗氧化作用。NaBu（0.3 mM）减轻了HO损伤的HepG2细胞中的细胞死亡和活性氧积累，并改善了多个抗氧化参数。NaBu通过提高p-GSK-3β（Ser9）水平抑制糖原合酶激酶-3β（GSK-3β），并促进核因子红细胞2相关因子2（Nrf2）的核转位，从而增加下游抗氧化酶的表达。连同促进过氧化物酶体增殖物激活受体γ共激活因子1α和线粒体DNA拷贝数，NaBu调节能量代谢和线粒体功能，减少糖酵解，增加β氧化，并增强三羧酸循环和氧化磷酸化。NaBu增加了线粒体锰超氧化物歧化酶和谷胱甘肽过氧化物酶活性。总之，NaBu通过调节Nrf2途径活性和线粒体功能保护HepG2细胞免受氧化应激。
