Polyol pathway exacerbated ischemia/reperfusion-induced injury in steatotic liver.

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.
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 NAD(P)(H) contents, redox status, and mitochondrial function; and (c) the flux through the caspase-dependent apoptosis pathway.
AR-inhibition in vivo markedly attenuated the I/R-induced liver injuries, maintained the homeostasis of NAD(P)(H) contents and redox status, and suppressed the caspase-dependent apoptosis pathway. Correspondingly, AR overexpression in vitro presented the opposite effects.
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.
AuthorsChanghe Zhang, Changjun Huang, Yuan Tian, Xiangcheng Li
JournalOxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2014 Pg. 963629 ( 2014) ISSN: 1942-0994 [Electronic] United States
PMID24967007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Polymers
  • polyol
  • Malondialdehyde
  • NADP
  • Aldehyde Reductase
  • Caspase 3
  • Aldehyde Reductase (antagonists & inhibitors, metabolism)
  • Animals
  • Apoptosis (drug effects)
  • Caspase 3 (metabolism)
  • Enzyme Inhibitors (pharmacology)
  • Fatty Liver (enzymology, etiology, pathology)
  • Hepatocytes (drug effects, pathology)
  • Intracellular Space (drug effects, metabolism)
  • Liver (drug effects, enzymology, pathology)
  • Male
  • Malondialdehyde (metabolism)
  • Membrane Potential, Mitochondrial (drug effects)
  • Metabolic Networks and Pathways (drug effects)
  • Mice, Inbred C57BL
  • NADP (metabolism)
  • Oxidation-Reduction (drug effects)
  • Polymers (metabolism)
  • Reperfusion Injury (complications, enzymology, pathology)

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