Sorbitol dehydrogenase inhibitor protects the liver from ischemia/reperfusion-induced injury via elevated glycolytic flux and enhanced sirtuin 1 activity

  • Authors:
    • Changhe Zhang
    • Xiangcheng Li
    • Qinhong Liu
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  • Published online on: October 21, 2014     https://doi.org/10.3892/mmr.2014.2715
  • Pages: 283-288
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Abstract

Sorbitol dehydrogenase (SDH), a key enzyme of the polyol pathway, has recently been demonstrated to have an important role in mediating tissue ischemia/reperfusion (I/R) injury. The present study investigated how this enzyme may affect the ischemic liver and the mechanism underlying its effect. Firstly, C57BL/6 mice were subjected to oral administration of CP‑470,711 (5 mg/kg body weight/day for five days) and 70% hepatic I/R. Next the present study further investigated the changes in liver function, histology, inflammation, apoptosis and necrosis; the cytosolic adenosine triphosphate (ATP) and nictotinamide adenine dinucleotide [NAD(H)] contents and the protein level of caspase 3 and sirtuin 1 (SIRT1). The data demonstrated that sorbitol dehydrogenase inhibitor (SDI)‑administration significantly alleviated I/R‑induced liver injury, palliated histological changes and lowered the level of hepatocyte apoptosis and necrosis. In addition, SDI‑pretreatment in ischemic liver markedly maintained the cytosolic ATP and NAD(H) proportion, enhanced SIRT1 and suppressed the activation of caspase 3 at the protein level. The findings in the present study revealed that the flux through SDH may render the liver more vulnerable to I/R-induced injury and interventions targeting this enzyme may provide a novel adjunctive approach to protect from severe tissue injury following liver ischemia.
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January-2015
Volume 11 Issue 1

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

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Spandidos Publications style
Zhang C, Li X and Liu Q: Sorbitol dehydrogenase inhibitor protects the liver from ischemia/reperfusion-induced injury via elevated glycolytic flux and enhanced sirtuin 1 activity. Mol Med Rep 11: 283-288, 2015
APA
Zhang, C., Li, X., & Liu, Q. (2015). Sorbitol dehydrogenase inhibitor protects the liver from ischemia/reperfusion-induced injury via elevated glycolytic flux and enhanced sirtuin 1 activity. Molecular Medicine Reports, 11, 283-288. https://doi.org/10.3892/mmr.2014.2715
MLA
Zhang, C., Li, X., Liu, Q."Sorbitol dehydrogenase inhibitor protects the liver from ischemia/reperfusion-induced injury via elevated glycolytic flux and enhanced sirtuin 1 activity". Molecular Medicine Reports 11.1 (2015): 283-288.
Chicago
Zhang, C., Li, X., Liu, Q."Sorbitol dehydrogenase inhibitor protects the liver from ischemia/reperfusion-induced injury via elevated glycolytic flux and enhanced sirtuin 1 activity". Molecular Medicine Reports 11, no. 1 (2015): 283-288. https://doi.org/10.3892/mmr.2014.2715