Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines

  • Authors:
    • Changxuan Shi
    • Yuanfang Wang
    • Jing Gao
    • Si Chen
    • Xiangqian Zhao
    • Chengchao Cai
    • Chang Guo
    • Longxin Qiu
  • View Affiliations

  • Published online on: June 30, 2017     https://doi.org/10.3892/mmr.2017.6895
  • Pages: 2767-2772
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Abstract

Aldose reductase (AR) expression is elevated in the livers of patients with alcoholic liver diseases. However, the role of AR in the development of alcoholic liver diseases remains unclear. The aim of the present study was to determine the effect of AR inhibition on ethanol‑induced hepatosteatosis in vivo and in vitro, and to identify possible underlying molecular mechanisms. Alcoholic fatty livers were induced in C57BL/6 mice by feeding the mice with Lieber‑DeCarli liquid diets. The expression of AR protein was elevated in the liver tissue of C57BL/6 mice fed with an ethanol diet and in mouse AML12 liver cells exposed to ethanol. In addition to the elevation in AR, hepatic steatosis was observed in ethanol diet‑fed mice, and this ethanol‑induced steatosis was significantly attenuated by inhibiting AR activity with a specific inhibitor, zopolrestat. The suppressive effect of AR inhibition was associated with decreased levels of hepatic lipoperoxides, decreased protein expression of hepatic cytochrome P450 2E1 (CYP2E1), increased phosphorylation of 5'‑AMP‑activated protein kinase (AMPK) and decreased mRNA expression of tumor necrosis factor‑α (TNF‑α). Treatment with the AR inhibitor attenuated the level of lipid accumulation and oxidative stress, activated AMPK, and suppressed the mRNA expression of TNF‑α, interleukin‑6 and transforming growth factor‑β1 in ethanol‑treated AML12 cells. The results of the present study demonstrated that inhibition of AR ameliorated alcoholic liver disease in vivo and in vitro, in part by activating AMPK, decreasing CYP2E1‑mediated oxidative stress and ameliorating the expression of pro‑inflammatory cytokines.
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September-2017
Volume 16 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Shi C, Wang Y, Gao J, Chen S, Zhao X, Cai C, Guo C and Qiu L: Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines. Mol Med Rep 16: 2767-2772, 2017.
APA
Shi, C., Wang, Y., Gao, J., Chen, S., Zhao, X., Cai, C. ... Qiu, L. (2017). Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines. Molecular Medicine Reports, 16, 2767-2772. https://doi.org/10.3892/mmr.2017.6895
MLA
Shi, C., Wang, Y., Gao, J., Chen, S., Zhao, X., Cai, C., Guo, C., Qiu, L."Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines". Molecular Medicine Reports 16.3 (2017): 2767-2772.
Chicago
Shi, C., Wang, Y., Gao, J., Chen, S., Zhao, X., Cai, C., Guo, C., Qiu, L."Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines". Molecular Medicine Reports 16, no. 3 (2017): 2767-2772. https://doi.org/10.3892/mmr.2017.6895