Ethyl pyruvate can alleviate alcoholic liver disease through inhibiting Nrf2 signaling pathway

Shen, Fei; Wang, Zhaohong; Liu, Wei; Ye, Liang

doi:10.3892/etm.2018.5925

Cited by 8 publications

(4 citation statements)

References 26 publications

(28 reference statements)

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“…In liver tissue, SOD levels in the ALD + Ex + NOXI group were lower than the ALD + NOXI group (p < 0.01), and MDA levels in the Eth + Ex group were higher than the Eth and Eth + Ex + NOXI groups (p < 0.05). It was confirmed that exercise or exercise combined with apocynin could reduce liver tissue peroxidation during the recovery period of ALD and can interfere with the body's ability to resist free radicals during alcohol consumption, which is similar to the conclusion obtained by Shen F [39].…”

Section: Discussionsupporting

confidence: 84%

Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6–p47phox Oxidative–Stress Axis

Cui

Xue

et al. 2022

Cells

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(1) Background: To explore the effect of exercise on the formation and recovery of alcoholic liver disease (ALD) and whether the IL-6–p47phox oxidative–stress axis is involved in that process. (2) Methods: Firstly, 23 six-week-old male C57BL/6J mice were randomly divided into the Con group, ALD group, ALD + NOXI group, ALD + Ex group, and ALD + Ex + NOXI group. The Liber–DeCarli alcoholic liquid diet was used for 6 weeks to establish the ALD mice model, and the Con group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet, and exercise intervention was started after the ALD model establishment and lasted for another 6 weeks, with or without administration of the NOX inhibitor apocynin by intraperitoneal injection on every exercise training day. Secondly, 28 mice were randomly divided into the Sed group, Eth group, Eth + Ex group and Eth + Ex + NOXI group. The Sed group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet and exercise intervention was started synchronously combined with or without administration of intraperitoneal apocynin injections on every exercise training day for 5 weeks. After each individual experiment was accomplished, physiological assessment and biochemical analysis of blood and tissue samples were examined. (3) Results: The levels of TG in serum and IL-6 protein content in liver tissue in the ALD group were significantly increased compared to the Con group (p < 0.05); compared with ALD, p47phox expression in muscle was increased significantly in the ALD + NOXI group (p < 0.05), and TG in serum decreased in the ALD + Ex group (p < 0.05). TG in serum, AST/ALT ratio, and IL-6 content in both liver and muscle decreased (p < 0.05) in the ALD + Ex + NOXI group with MDA in muscle significantly increased (p < 0.01). The AST/ALT ratio, TG in serum, SOD in liver, and p47phox in both liver and muscle in the ALD + Ex + NOXI group were significantly decreased compared with the ALD + NOXI group (p < 0.01). Compared with the ALD + Ex group, the liver index and HDL-C levels in serum were decreased (p < 0.05) in the ALD + Ex + NOXI group. The degree of hepatocyte steatosis and inflammatory infiltration were ameliorated after exercise intervention. In the Eth group, the relative epididymal fat content, HDL-C level, and AST/ALT ratio were significantly decreased, and TG and gp91phox in liver were significantly higher than in the Sed group (p < 0.05, p < 0.01). Compared with the Eth group, the AST/ALT ratio, MDA in the liver, and NOX4 and p47phox protein expression in the liver were significantly increased, and body weight decreased significantly in the Eth + Ex group (p < 0.05, p < 0.01), as did TG in the liver and MDA in muscle. In the th + Ex + NOXI group, gp91phox expression in the liver and body weight were significantly decreased (p < 0.05, p < 0.01). In the Eth + Ex + NOXI group, the ratio of AST/ALT and MDA in muscle were increased when compared with the Eth + Ex group, and the protein expression of gp91phox and p47phox were much lower (p < 0.01). (4) Conclusions: 6 weeks of exercise intervention during the recovery phase of ALD ameliorates hepatocyte damage and dyslipidemia through the IL-6–p47phox oxidative–stress axis, and applying a NOX inhibitor in combination could optimize this. However, drinking alcohol during exercise exacerbates dyslipidemia and oxidative stress, with hepatocyte IL-6–p47phox downregulated.

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Section: Discussionsupporting

confidence: 84%

Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6–p47phox Oxidative–Stress Axis

Cui

Xue

et al. 2022

Cells

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“…Furthermore, recent advances indicated that activation of the Nrf2 pathway was protective in alcohol-induced liver fibrosis and hepatotoxicity, whereas knockdown of Nrf2 was associated with enhanced alcohol-induced hepatocyte necroptosis (Song et al, 2015; Lu et al, 2016; Ni et al, 2017). By contrast, a more recent study demonstrated that ethyl pyruvate, which has multi-effects including antibacterial, anti-inflammatory, antiviral, vasodilatory, antioxidant, and antiapoptotic effects, decreases ALT, AST, hepatic morphological changes, triglycerides, free fatty acids, and the expression of proinflammatory factors and increases the expression of anti-inflammatory factors and peroxisome proliferator-activated receptor-α mRNA which through downregulation of the ROS–Nrf2 signaling pathway, thereby alleviating ALD in mice (Fawcett et al, 1999; Harding et al, 2000; Shen F. et al, 2018). Taken together, these evidences showed that Nrf2 activation plays essential protective role in the development of ALD and that simultaneous downregulation of Nrf2 with ROS and VLDLR may also be effective in the amelioration of ALD (Figure 2).…”

Section: Activation Of Nrf2 Ameliorates Alcoholic Liver Diseasementioning

confidence: 99%

The Role of Nrf2 in Liver Disease: Novel Molecular Mechanisms and Therapeutic Approaches

et al. 2019

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Oxidative stress and inflammation are the most important pathogenic events in the development and progression of liver diseases. Nuclear erythroid 2-related factor 2 (Nrf2) is the master regulator of the cellular protection via induction of anti-inflammatory, antioxidant, and cyto-protective genes expression. Multiple studies have shown that activation or suppression of this transcriptional factor significantly affect progression of liver diseases. Comprehensive understanding the roles of Nrf2 activation/expression and the outcomes of its activators/inhibitors are indispensable for defining the mechanisms and therapeutic strategies against liver diseases. In this current review, we discussed recent advances in the function and principal mechanisms by regulating Nrf2 in liver diseases, including acute liver failure, hepatic ischemia–reperfusion injury (IRI), alcoholic liver disease (ALD), viral hepatitis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC).

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“…Oxidative stress triggers macrophages to release pro‐inflammatory cytokines (Chen, Yao, et al, 2020; Li et al, 2021). Basal amounts of TNF‐α and MCP‐1 are produced in the liver under physiological conditions, and increased in alcoholic liver injury mice (Shen et al, 2018; Xu et al, 2022). MCP‐1 belongs to chemokine family, which is a key factor in inflammatory process.…”

Section: Resultsmentioning

confidence: 99%

Zhenjiang aromatic vinegar prevents the alcohol liver disease in mice via autophagy

Zhao,

Xia,

Qiang

et al. 2023

eFood

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Alcoholic liver disease (ALD) is an ignored global issue of public health. It is urgent for searching bioactive foods to prevent ALD. Zhenjiang aromatic vinegar (ZAV) contained antioxidant compounds, including polyphenols, flavonoids, and melanoidins. The mechanism of ZAV on preventing acute liver injury was evaluated in alcohol‐treated mice. Our results showed that ZAV ameliorated morphological damage by hematoxylin and eosin and Oil Red O staining in alcohol‐treated liver. ZAV relieved symptoms of ALD, which presented as decreased serum triacylglycerol, total cholesterol, alanine transaminase, and aspartate aminotransferase levels. In addition, ZAV treatment inhibited hepatic oxidative stress levels by downregulating reactive oxygen species generation, and the oxidative products (malonaldehyde, 4‐hydroxynonenal, and 8‐hydroxydeoxyguanosine), and upregulating catalase, superoxide dismutase, glutathione, and glutathione peroxidase. ZAV further reduced production of tumor necrosis factor‐α and monocyte chemoattractant protein‐1, and elevated levels of interleukin‐4 and transforming growth factor‐β indicating the inhibition of alcohol‐induced inflammation. Furthermore, ZAV treatment increased expression levels of autophagy‐associated proteins in ALD mice by western blot, which participated in anti‐ALD effect of ZAV. These findings demonstrate that ZAV could be an alternative for ALD intervention by regulating oxidative stress and autophagy.

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Ethyl pyruvate can alleviate alcoholic liver disease through inhibiting Nrf2 signaling pathway

Cited by 8 publications

References 26 publications

Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6–p47phox Oxidative–Stress Axis

Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6–p47phox Oxidative–Stress Axis

The Role of Nrf2 in Liver Disease: Novel Molecular Mechanisms and Therapeutic Approaches

Zhenjiang aromatic vinegar prevents the alcohol liver disease in mice via autophagy

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