Simultaneous liver and lung injury following gut ischemia is mediated by xanthine oxidase.
We have previously shown that gut ischemia/reperfusion (I/R) causes simultaneous liver and lung dysfunction and that neutrophils play a critical role in this process. The purpose of this study was to ascertain whether xanthine oxidase (XO) was likewise operational. Normal and XO-inactivated rats (given a tungsten-enriched, molybdenum-depleted diet for 3 weeks) underwent 45 minutes of occlusion of the superior mesenteric artery, and control rats were subjected to a sham laparotomy. After zero and six hours of reperfusion, blood was sampled and livers and lungs harvested. Iodine-125-labeled albumin leak was used as a marker for pulmonary and liver capillary permeability barrier function, and serum acetoacetate/3-hydroxybutyrate (AcAc/3-OHB) levels as an index of hepatic mitochondrial redox state. Gut ischemia/six hours of reperfusion (I/R) increased the 125I albumin lung/blood ratio and the 125I albumin liver/blood ratio; AcAc/3-OHB levels decreased significantly. Xanthine oxidase activation eliminated the observed lung and liver capillary leak as well as the hepatic metabolic derangement induced by gut I/R. In conclusion, the simultaneous lung and liver dysfunction produced by gut I/R is mediated by XO.
Poggetti
R S
RS
Department of Surgery, Denver General Hospital, Colorado.
Moore
F A
FA
Moore
E E
EE
Koeike
K
K
Banerjee
A
A
D000818:Animals; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D007511:Ischemia / Q000150:complications*; D008099:Liver / Q000098:blood supply*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D012711:Serum Albumin, Radio-Iodinated; D014969:Xanthine Oxidase / Q000502:physiology*
D012711:Serum Albumin, Radio-Iodinated; D014969:Xanthine Oxidase