NEUTROPHIL INFILTRATION AS AN IMPORTANT FACTOR IN LIVER ISCHEMIA AND REPERFUSION INJURY - MODULATING EFFECTS OF FK506 AND CYCLOSPORINE

To examine the role of neutrophils, their presence and the degree of i nfiltration, as important determinants of ischemia and reperfusion inj ury of the liver, male Sprague-Dawley rats were subjected to 60 and 90 min of total-liver ischemia. The presence of neutrophils, assessed by the measurement of liver tissue myeloperoxidase (MPO), and the degree of neutrophil liver infiltration, determined by the naphthol AS-D chl oroacetate esterase technique, correlated well with animal survival an d response to FK506 and cyclosporine administration. Lipid peroxidatio n, measured by the malondialdehyde (MDA) test in liver tissue, was ano ther factor closely linked with liver function and survival. Pretreatm ent with FK506 (0.3 mg/kg) and CsA (5 mg/kg) was given at 4 hr and 1 h r before ischemia and at the time of reperfusion. Control ischemic ani mals showed increased neutrophil liver infiltration, high MPO and MDA liver levels, and diminished overall survival. FK506 and CsA-treated a nimals had better survival and diminished neutrophil liver infiltratio n, as well as MPO and MDA levels. The mechanism by which FK506 and CsA protected the animals from severe liver ischemic injury is unknown. O ur data indicated that the presence and the degree of infiltration of neutrophils were important components of liver ischemia/reperfusion in jury in the rat. So it is possible that one of the fundamental effects of the FK506 and CsA might be through the inhibition of the presence and infiltration of neutrophils in liver tissue.