title: Ischemia-Reperfusion Injury in Fatty Liver Is Mediated by Activated NADPH Oxidase 2 in Rats.
abstract: BACKGROUND
  Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers.
  
  
  METHODS
  Rats were fed a methionine and choline-deficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion.
  
  
  RESULTS
  The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), TNFα, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2'-deoxyguanosine, TNFα, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers.
  
  
  CONCLUSIONS
  Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kimura
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takeishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Itoh
authors.forename: Norifumi
authors.initials: N
authors.lastname: Harimoto
authors.forename: Toru
authors.initials: T
authors.lastname: Ikegami
authors.forename: Hideaki
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002478:Cells, Cultured; D002796:Choline Deficiency / Q000150:complications; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005234:Fatty Liver / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D024243:HMGB1 Protein / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008715:Methionine / Q000172:deficiency; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009336:Necrosis; D018384:Oxidative Stress; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018836:Inflammation Mediators; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008715:Methionine; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D003849:Deoxyguanosine