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NEUTROPHIL INFILTRATION AS AN IMPORTANT FACTOR IN LIVER ISCHEMIA AND REPERFUSION INJURY
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1993
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Lipid PeroxidationImmunologyPathologyNeutrophil InfiltrationLiver FunctionMda Liver LevelsRedox BiologyOxidative StressInflammationHematologyLiver InfiltrationSepsisToxicologyHepatotoxicityHealth SciencesLiver PhysiologyHepatology InflammationVascular BiologyMetabolomicsReperfusion InjuryPharmacologyDrug-induced Liver InjuryLiverHepatologyPhysiologyAcute Liver FailureLiver DiseaseMetabolismMedicine
The protective mechanism of FK506 and cyclosporine A against severe liver ischemia/reperfusion injury remains unclear. This study aimed to determine whether neutrophil presence and infiltration drive liver ischemia/reperfusion injury in rats. Male Sprague‑Dawley rats underwent 60–90 min total liver ischemia, with pretreatment of FK506 (0.3 mg/kg) or CsA (5 mg/kg) 4 h and 1 h before ischemia and at reperfusion; neutrophil infiltration was quantified by myeloperoxidase and esterase staining, and lipid peroxidation by malondialdehyde levels. In untreated animals, neutrophil infiltration, MPO, and MDA levels were elevated and survival was reduced, whereas FK506 and CsA treatment lowered these markers and improved survival, indicating neutrophil infiltration is a key determinant of injury.
To examine the role of neutrophils, their presence and the degree of infiltration, as important determinants of ischemia and reperfusion injury 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 chloroacetate esterase technique, correlated well with animal survival and response to FK506 and cyclosporine administration. Lipid peroxidation, measured by the malondialdehyde (MDA) test in liver tissue, was another factor closely linked with liver function and survival. Pretreatment with FK506 (0.3 mg/kg) and CsA (5 mg/kg) was given at 4 hr and 1 hr before ischemia and at the time of reperfusion. Control ischemic animals showed increased neutrophil liver infiltration, high MPO and MDA liver levels, and diminished overall survival. FK506 and CsA-treated animals had better survival and diminished neutrophil liver infiltration, as well as MPO and MDA levels. The mechanism by which FK506 and CsA protected the animals from severe liver ischemic injury is unknown. Our data indicated that the presence and the degree of infiltration of neutrophils were important components of liver ischemia/reperfusion injury 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.