In situ determination by surface chemiluminescence of temporal relationships between evolving warm ischemia-reperfusion injury in rat liver and phagocyte activation and recruitment

Abstract

Liver ischemia-reperfusion is characterized by an increased oxygen-dependent free radical chain-reaction rate and an increased steady-state concentration of reactive oxygen species. The aim of this study was to evaluate the in situ generation of reactive oxygen species and its relationship with phagocyte activation and recruitment in reperfused rat liver. Rat livers were subjected to 2 hours of selective lobular ischemia and reperfusion for up to 12 hours. The following parameters were determined: in situ liver chemiluminescence, understood to reflect the tissue steady-state concentration of singlet oxygen ( 1 O 2 ); myeloperoxidase tissue activity; the number of neutrophils; and the degree of necrosis. An early chemiluminescence burst was measured after 30 minutes of blood reflow (early phase of oxidative stress), followed by a relapse and a further increase after 4 to 12 hours of reperfusion (late phase of oxidative stress). Both early and late phases were modified by pretreatment with gadolinium chloride (GdCl 3 ), pointing to a key role of the Kupffer cells. Neutrophils infiltrated into the liver, myeloperoxidase activity, in situ chemiluminescence, and necrosis were found to be strongly correlated over the 4-to 12-hour reperfusion period (r ‫؍‬ .960; average of the 4 correlation coefficients). Together with resident phagocytes, neutrophil recruitment and activation appear to provide a major contribution to the increase of oxygendependent free-radical reactions and amplification of liver reperfusion damage. Surface chemiluminescence appears to properly describe the in situ and in vivo progressive organization of the acute inflammatory response with phagocytemediated liver injury. (HEPATOLOGY 2000;31:622-632.)

Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: Prevention of reperfusion injury

“…Irreversible hepatic damage was induced in the rat by reperfusion of ischaemic liver (1 h of ischaemia and 12 h of reperfusion), as described in ref. 15. RI injury was evaluated by alanin-aminotransferase levels in plasma obtained from posterior cava vein 12 h after reperfusion by using a commercial kit (Sigma).…”

The Radical Scavenger Edaravone (3-Methyl-1-phenyl-2-pyrazolin-5-one) Reacts with a Pterin Derivative and Produces a Cytotoxic Substance That Induces Intracellular Reactive Oxygen Species Generation and Cell Death

“…Singlet oxygen is known to induce neuronal and hepatic cell death (Cutrìn et al, 2000;Petrat et al, 2003;Valencia and Moran, 2004). Furthermore, 1 O 2 is tumoricidal and plays an important role in anticancer photodynamic therapy (Dougherty et al, 1998;Dolmans et al, 2003).…”

Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning

“…A considerable number of experimental studies have indicated that ischemia/reperfusion-induced liver injury occurs in a biphasic manner [5,8,9]. Data obtained by several different research groups suggest that in both early and late phases of reperfusion injury, oxidative stress is one of the main pathogenic mechanisms [5,10,11].…”

“…Activation of neutrophils has been implicated in the hepatic microvascular dysfunction and parenchymal damage associated with ischemia/reperfusion [8,9,11,12,15,47,48]. This is based on the observation that preventing neutrophil influx into tissues, either by depleting the number of circulating neutrophils or by preventing neutrophil adhesion, significantly reduces microvascular dysfunction and organ injury in animal models of ischemia/reperfusion damage [49,50].…”