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Oxidative Medicine and Cellular LongevityVolume 2014 2014, Article ID 963629, 9 pages

Research ArticleDepartment of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

Received 20 January 2014; Revised 14 April 2014; Accepted 16 April 2014; Published 21 May 2014

Academic Editor: Felipe Dal-Pizzol

Copyright © 2014 Changhe Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. The polyol pathway, a bypass pathway of glucose metabolism initiated by aldose reductase AR, has been shown to play an important role in mediating tissue ischemia-reperfusion I-R impairment recently. Here, we investigated how and why this pathway might affect the fatty liver following I-R. Methods. Two opposite models were created: mice with high-fat-diet-induced liver steatosis were treated with aldose reductase inhibition ARI and subsequent I-R; and AR-overexpressing L02 hepatocytes were sequentially subjected to steatosis and hypoxia-reoxygenation. We next investigated a the hepatic injuries, including liver function, histology, and hepatocytes apoptosis-necrosis; b the NADPH contents, redox status, and mitochondrial function; and c the flux through the caspase-dependent apoptosis pathway. Results. AR-inhibition in vivo markedly attenuated the I-R-induced liver injuries, maintained the homeostasis of NADPH contents and redox status, and suppressed the caspase-dependent apoptosis pathway. Correspondingly, AR overexpression in vitro presented the opposite effects. Conclusion. The flux through the polyol pathway may render steatotic liver greater vulnerability to I-R. Interventions targeting this pathway might provide a novel adjunctive approach to protect fatty liver from ischemia.

Autor: Changhe Zhang, Changjun Huang, Yuan Tian, and Xiangcheng Li

Fuente: https://www.hindawi.com/


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