Lung injury after hepatoenteric ischemia-reperfusion: role of xanthine oxidase.
Oxidant stress plays a major role in the pathophysiologic processes associated with ischemia-reperfusion injury. Xanthine oxidase (XO) is often implicated as a significant source of oxidants and increases in the circulation after hepatoenteric ischemia-reperfusion. We hypothesized that pulmonary injury is associated with hepatic ischemia-reperfusion resulting from descending thoracic aorta occlusion-reperfusion (AoOR). We also proposed that this remote pulmonary injury is attenuated through inactivation of circulating and tissue XO by tungstate, implicating an XO-dependent mechanism. Aortic occlusion was established in rabbits (standard or tungstate diet) for 40 min by 2 h reperfusion. Sham operated rabbits (standard or tungstate diet) served as controls. Hepatic reperfusion injury, as manifested by release of the hepatocellular enzyme alanine aminotransferase (ALT), was markedly increased after AoOR. Suprarenal-infrahepatic occlusion failed to increase ALT release. Tungstate pretreatment significantly (p < 0.05) reduced XO activity and ameliorated liver and intestinal injury (p < 0.05). Lung injury, manifested by increased bronchoalveolar lavage (BAL) protein concentration, BAL lactate dehydrogenase (LDH) activity and increased lung edema was significantly associated with liver injury (p < 0.05) and circulating XO activity (p < 0.001). XO inactivation significantly decreased BAL protein concentration, BAL LDH activity, and lung edema (p < 0.05). We conclude that remote pulmonary injury is significantly influenced by the extent of liver injury and circulating XO activity.
Department of Anesthesiology, University of Alabama at Birmingham, USA.
V G
VG
Nielsen
S
S
Tan
A
A
Weinbroum
A T
AT
McCammon
P N
PN
Samuelson
S
S
Gelman
D A
DA
Parks
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism*; D017973:Tungsten Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000502:physiology
D017973:Tungsten Compounds; C025399:sodium tungstate(VI); D014969:Xanthine Oxidase; D000410:Alanine Transaminase