Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
September-2017 Volume 16 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2017 Volume 16 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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 / Copyright

    Affiliations: Department of Biological Science and Technology, School of Life Sciences, Longyan University, Longyan, Fujian 364012, P.R. China
  • Pages: 2767-2772
    |
    Published online on: June 30, 2017
       https://doi.org/10.3892/mmr.2017.6895
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Ishii H, Kurose I and Kato S: Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress. J Gastroenterol Hepatol. 12:S272–S282. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Kawaratani H, Tsujimoto T, Douhara A, Takaya H, Moriya K, Namisaki T, Noguchi R, Yoshiji H, Fujimoto M and Fukui H: The effect of inflammatory cytokines in alcoholic liver disease. Mediators Inflamm. 2013:4951562013. View Article : Google Scholar : PubMed/NCBI

3 

Hers HG: Aldose reductase. Biochim Biophys Acta. 37:120–126. 1960.(In French). View Article : Google Scholar : PubMed/NCBI

4 

Nishimura-Yabe C: Aldose reductase in the polyol pathway: A potential target for the therapeutic intervention of diabetic complications. Nihon Yakurigaku Zasshi. 111:137–145. 1998.(In Japanese). View Article : Google Scholar : PubMed/NCBI

5 

Brown KE, Broadhurst KA, Mathahs MM, Kladney RD, Fimmel CJ, Srivastava SK and Brunt EM: Immunodetection of aldose reductase in normal and diseased human liver. Histol Histopathol. 20:429–436. 2005.PubMed/NCBI

6 

O'Connor T, Ireland LS, Harrison DJ and Hayes JD: Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. Biochem J. 343:487–504. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Qiu L, Lin J, Xu F, Gao Y, Zhang C, Liu Y, Luo Y and Yang JY: Inhibition of aldose reductase activates hepatic peroxisome proliferator-activated receptor-α and ameliorates hepatosteatosis in diabetic db/db mice. Exp Diabetes Res. 2012:7897302012. View Article : Google Scholar : PubMed/NCBI

8 

Qiu L, Lin J, Ying M, Chen W, Yang J, Deng T, Chen J, Shi D and Yang JY: Aldose reductase is involved in the development of murine diet-induced nonalcoholic steatohepatitis. PLoS One. 8:e735912013. View Article : Google Scholar : PubMed/NCBI

9 

Chen T, Shi D, Chen J, Yang Y, Qiu M, Wang W and Qiu L: Inhibition of aldose reductase ameliorates diet-induced nonalcoholic steatohepatitis in mice via modulating the phosphorylation of hepatic peroxisome proliferator-activated receptor α. Mol Med Rep. 11:303–308. 2015.PubMed/NCBI

10 

Peng Z, Borea PA, Varani K, Wilder T, Yee H, Chiriboga L, Blackburn MR, Azzena G, Resta G and Cronstein BN: Adenosine signaling contributes to ethanol-induced fatty liver in mice. J Clin Invest. 119:582–594. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Lieber CS, DeCarli LM and Sorrell MF: Experimental methods of ethanol administration. Hepatology. 10:501–510. 1989. View Article : Google Scholar : PubMed/NCBI

13 

Leung TM and Nieto N: CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. J Hepatol. 58:395–398. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Lu Y and Cederbaum AI: CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med. 44:723–738. 2008. View Article : Google Scholar : PubMed/NCBI

15 

You M, Matsumoto M, Pacold CM, Cho WK and Crabb DW: The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology. 127:1798–1808. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Sid B, Verrax J and Calderon PB: Role of AMPK activation in oxidative cell damage: Implications for alcohol-induced liver disease. Biochem Pharmacol. 86:200–209. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Barry RE: Role of acetaldehyde in the pathogenesis of alcoholic liver disease. Br J Addict. 83:1381–1386. 1988. View Article : Google Scholar : PubMed/NCBI

18 

Vander Jagt DL and Hunsaker LA: Substrate specificity of reduced and oxidized forms of human aldose reductase. Adv Exp Med Biol. 328:279–288. 1993. View Article : Google Scholar : PubMed/NCBI

19 

Vander Jagt DL, Kolb NS, Vander Jagt TJ, Chino J, Martinez FJ, Hunsaker LA and Royer RE: Substrate specificity of human aldose reductase: Identification of 4-hydroxynonenal as an endogenous substrate. Biochim Biophys Acta. 1249:117–126. 1995. View Article : Google Scholar : PubMed/NCBI

20 

Zhang C, Huang C, Tian Y and Li X: Polyol pathway exacerbated ischemia/reperfusion-induced injury in steatotic liver. Oxid Med Cell Longev. 2014:9636292014. View Article : Google Scholar : PubMed/NCBI

21 

Ruef J, Liu SQ, Bode C, Tocchi M, Srivastava S, Runge MS and Bhatnagar A: Involvement of aldose reductase in vascular smooth muscle cell growth and lesion formation after arterial injury. Arterioscler Thromb Vasc Biol. 20:1745–1752. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Tracey WR, Magee WP, Ellery CA, MacAndrew JT, Smith AH, Knight DR and Oates PJ: Aldose reductase inhibition alone or combined with an adenosine A (3) agonist reduces ischemic myocardial injury. Am J Physiol Heart Circ Physiol. 279:H1447–H1452. 2000.PubMed/NCBI

23 

Morimoto M, Hagbjörk AL, Nanji AA, Ingelman-Sundberg M, Lindros KO, Fu PC, Albano E and French SW: Role of cytochrome P4502E1 in alcoholic liver disease pathogenesis. Alcohol. 10:459–464. 1993. View Article : Google Scholar : PubMed/NCBI

24 

Viollet B, Guigas B, Leclerc J, Hébrard S, Lantier L, Mounier R, Andreelli F and Foretz M: AMP-activated protein kinase in the regulation of hepatic energy metabolism: From physiology to therapeutic perspectives. Acta Physiol (Oxf). 196:81–98. 2009. View Article : Google Scholar : PubMed/NCBI

25 

An L, Wang X and Cederbaum AI: Cytokines in alcoholic liver disease. Arch Toxicol. 86:1337–1348. 2012. View Article : Google Scholar : PubMed/NCBI

26 

McClain CJ and Cohen DA: Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. Hepatology. 9:349–351. 1989. View Article : Google Scholar : PubMed/NCBI

27 

Endo M, Masaki T, Seike M and Yoshimatsu H: TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c). Exp Biol Med (Maywood). 232:614–621. 2007.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team