title: Polyol pathway exacerbated ischemia/reperfusion-induced injury in steatotic liver.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Changhe
authors: C
authors: Zhang
authors: Department of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Changjun
authors: C
authors: Huang
authors: Department of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Yuan
authors: Y
authors: Tian
authors: Department of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Xiangcheng
authors: 0000-0003-2987-0782
authors: X
authors: Li
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005234:Fatty Liver / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011108:Polymers / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications* / Q000201:enzymology / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D011108:Polymers; C024617:polyol; D008315:Malondialdehyde; D009249:NADP; D000449:Aldehyde Reductase; D053148:Caspase 3