Mechanism for enterohepatic injury caused by circulatory disturbance of hepatic vessels in the rat.
We reported previously that a transient occlusion followed by reperfusion of the portal vein and the hepatic artery of the rat significantly decreased the transhepatic transport of a cholephilic compound, and that this decrease was prevented by pretreating animals with poly(styrene co-maleic acid butyl ester)-conjugated superoxide dismutase (SM-SOD). To elucidate the mechanism for oxidative injury of the liver and the site for the generation of superoxide radicals, the effect of a portosystemic bypass on the liver function was examined in the rat whose hepatic vessels were temporarily occluded. A portosystemic bypass inhibited the reperfusion-induced decrease in hepatic transport of bromosulfophthalein as effectively as did SM-SOD. Kinetic analysis using 125I-labeled albumin revealed that the permeability of the small intestine markedly increased after a transient occlusion. The increase in intestinal permeability was also inhibited either by SM-SOD or by the portosystemic bypass. Xanthine oxidase activity in portal plasma markedly increased during occlusion and reperfusion, while it remained within normal ranges in the bypassed group. Thus, superoxide radical, and/or its metabolite(s), might play a critical role in increasing the intestinal permeability and in the pathogenesis of reperfusion-induced liver injury.
Kawamoto
S
S
Department of Biochemistry, Kumamoto University Medical School, Japan.
Tashiro
S
S
Miyauchi
Y
Y
Inoue
M
M
D000818:Animals; D001386:Azides / Q000494:pharmacology; D001794:Blood Pressure; D002374:Catalase / Q000494:pharmacology; D004764:Enterohepatic Circulation; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008163:Luminescent Measurements; D008297:Male; D011170:Portasystemic Shunt, Surgical / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology*; D012709:Serum Albumin / Q000378:metabolism; D019810:Sodium Azide; D013448:Sulfobromophthalein / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000097:blood; D015054:Zymosan / Q000494:pharmacology
D001386:Azides; D012709:Serum Albumin; D013448:Sulfobromophthalein; D015054:Zymosan; D019810:Sodium Azide; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase