Hepatic liver ischemia/reperfusion injury

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Abstract

We read with great interest the recent excellent and comprehensive review of hepatic ischemia/reperfusion injury (IRI) by Abu-Amara et al.1 The review is focused, in part, on the role of reactive oxygen species (ROS) in the regulation of hepatic IRI. We agree with Abu-Amara et al. and other authors2 who have suggested that liver resident macrophages or Kupffer cell–derived ROS are key players in initiating and propagating cellular damage in the early phase of hepatic IRI. However, some studies have shown that depletion of Kupffer cells does not ameliorate hepatocyte damage after IRI.3 Our recent study has conclusively shown that hepatocytes are also important sources of ROS during hepatic IRI.4 This latter point has not been included in the review by Abu-Amara et al. Indeed, hepatocytes may also be important sources of ROS along with Kupffer cells and neutrophils in the late stage of hepatic IRI.2 We suggest that models of hepatic IRI should include the significant contribution of hepatocytes to the evolution of the injury. Hepatocytes are likely to play at least 2 key roles in hepatic IRI. First, hepatocytes generate significant levels of intracellular ROS during hypoxia and hypoxia/reoxygenation.4 The subsequent release of intracellular ROS by necrotic hepatocytes into the liver parenchyma will perpetuate hepatocyte cell death.5 Second, hepatocytes can secrete proinflammatory cytokines and chemokines during hepatic inflammation, which can then propagate liver injury.6 Therefore, we suggest that in the current model of hepatic IRI, hepatocytes should not be considered bystanders and targets of the injury. They should be seen as active participants in IRI in both the ischemic and reperfusion phases. This will improve our understanding of this complex and multifactorial injury. Ricky H. Bhogal MRCS.Ed.*, Rupesh Sutaria MRCS. , Simon C. Afford Ph.D., FRC.Path. , * Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom, MRC Centre for Immune Regulation, University of Birmingham Institute of Clinical Science, Birmingham, United Kingdom.

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