Abstract | 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 NAD(P)(H) 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 NAD(P)(H) 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.
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Authors | Changhe Zhang, Changjun Huang, Yuan Tian, Xiangcheng Li |
Journal | Oxidative medicine and cellular longevity
(Oxid Med Cell Longev)
Vol. 2014
Pg. 963629
( 2014)
ISSN: 1942-0994 [Electronic] United States |
PMID | 24967007
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Polymers
- polyol
- Malondialdehyde
- NADP
- Aldehyde Reductase
- Caspase 3
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Topics |
- 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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