Primary role of Kupffer cell–hepatocyte communication in the expression of oxidative stress in the post-ischaemic liver

Cutrìn, Juan Carlos; Llesuy, Susana; Boveris, Alberto

doi:10.1002/(sici)1099-0844(199803)16:1<65::aid-cbf772>3.0.co;2-u

Cited by 32 publications

(1 citation statement)

References 35 publications

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“…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]. The early phase, which occurs between 0.5 and 4 h from the onset of reperfusion, appears to be associated with the generation of reactive oxygen species (ROS) by the activated Kupffer cell and by the reduced respiratory chains in hepatocytes and endothelial sinusoidal cells [5,8,[12][13][14]. Furthermore, during this initial period, neutrophils are primed and activated.…”

Section: What Is Hepatic Microvascular Dysfunction?mentioning

confidence: 99%

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

Cutrn

Perrelli

Cavalieri

et al. 2002

Free Radical Biology and Medicine

150

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Abstract-Hepatic ischemia/reperfusion injury has immediate and deleterious effects on the outcome of patients after liver surgery. The precise mechanisms leading to the damage have not been completely elucidated. However, there is substantial evidence that the generation of oxygen free radicals and disturbances of the hepatic microcirculation are involved in this clinical syndrome. Microcirculatory dysfunction of the liver seems to be mediated by sinusoidal endothelial cell damage and by the imbalance of vasoconstrictor and vasodilator molecules, such as endothelin (ET), reactive oxygen species (ROS), and nitric oxide (NO). This may lead to no-reflow phenomenon with release of proinflammatory cytokines, sinusoidal plugging of neutrophils, oxidative stress, and as an ultimate consequence, hypoxic cell injury and parenchymal failure. An inducible potent endogenous mechanism against ischemia/reperfusion injury has been termed ischemic preconditioning. It has been suggested that preconditioning could inhibit the effects of different mediators involved in the microcirculatory dysfunction, including endothelin, tumor necrosis factor-␣, and oxygen free radicals. In this review, we address the mechanisms of liver microcirculatory dysfunction and how ischemic preconditioning could help to provide new surgical and/or pharmacological strategies to protect the liver against reperfusion damage.

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Section: What Is Hepatic Microvascular Dysfunction?mentioning

confidence: 99%

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

Cutrn

Perrelli

Cavalieri

et al. 2002

Free Radical Biology and Medicine

150

View full text Add to dashboard Cite

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Ischaemic preconditioning modulates the activity of Kupffer cells during in vivo reperfusion injury of rat liver

Cavalieri¹,

Perrelli²,

Aragno³

et al. 2003

Cell Biochemistry & Function

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This work was performed to elucidate further the main cellular events underlying the protective effect of ischaemic preconditioning in an in vivo rat liver model of 90 min ischaemia followed by 30 min reperfusion. A significant attenuation of the various aspects of post-ischaemic injury, namely necrosis and the levels of hydrogen peroxide and 5- and 15-hydroperoxyeicosatetraenoic acids, was afforded by the prior application of a short cycle of ischaemia/reperfusion (10 + 10 min) or when rats were previously treated with gadolinium chloride. However, when preconditioning was applied on Kupffer cell-depleted livers, no additional level of ischaemic tolerance was obtained. In terms of cellular pathology, this result could be suggestive of Kupffer cells as the target of the preconditioning phenomenon during the warm ischaemia/reperfusion injury. Accordingly, modulation of Kupffer cell activity was associated with a well-preserved hepatocyte integrity, together with low levels of pro-oxidant generation during reperfusion. As activated Kupffer cells can generate and release potentially toxic substances, their modulation by ischaemic preconditioning could help to provide new surgical and/or pharmacological strategies to protect the liver against reperfusion damage.

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

et al. 2000

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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.)

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Primary role of Kupffer cell–hepatocyte communication in the expression of oxidative stress in the post-ischaemic liver

Cited by 32 publications

References 35 publications

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

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

Ischaemic preconditioning modulates the activity of Kupffer cells during in vivo reperfusion injury of rat liver

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

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