Oxidant stress and potentiation of ischemia/reperfusion injury to the perfused rat liver by human polymorphonuclear leukocytes.
The accumulation and activation of polymorphonuclear leukocytes in the liver may play an important role in liver damage following ischemia and reperfusion. To study the effects of polymorphonuclear leukocytes on hepatic function, human polymorphonuclear leukocytes were infused into perfused rat livers. Infusion of polymorphonuclear leukocytes into continuously oxygenated livers led to an increased consumption of oxygen by the perfused liver which paralleled the production of superoxide anion radicals by activated polymorphonuclear leukocytes. The increased use of oxygen was followed by a decrease in the sinusoidal efflux of glutathione and a marked increase in the biliary excretion of glutathione disulfide, indicating that polymorphonuclear leukocytes were activated within the liver, and created a potentially deleterious oxidant stress. When polymorphonuclear leukocytes were infused into rat livers that had been subjected to 45 min of warm ischemia followed by reperfusion, the release of lactate dehydrogenase upon reperfusion of ischemic liver was significantly higher from livers exposed to polymorphonuclear leukocytes than from livers subjected to the same period of ischemia without leukocytes. This indicates that polymorphonuclear leukocytes potentiate ischemia/reperfusion injury. The present in vitro system provides a model to study pharmacological interventions designed to modulate the potentially deleterious interactions of polymorphonuclear leukocytes with the liver.
Bilzer
M
M
Department of Clinical Pharmacology, University of Berne, Switzerland.
Lauterburg
B H
BH
D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood*
D010100:Oxygen