| Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation. | |
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MedLine Citation:
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PMID: 21031546 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Increasing evidence shows that reactive oxygen species (ROS) may be critical mediators of liver damage during the relative hypoxia of ischemia/reperfusion injury (IRI) associated with transplant surgery or of the tissue microenvironment created as a result of chronic hepatic inflammation or infection. Much work has been focused on Kupffer cells or liver resident macrophages with respect to the generation of ROS during IRI. However, little is known about the contribution of endogenous hepatocyte ROS production or its potential impact on the parenchymal cell death associated with IRI and chronic hepatic inflammation. For the first time, we show that human hepatocytes isolated from nondiseased liver tissue and human hepatocytes isolated from diseased liver tissue exhibit marked differences in ROS production in response to hypoxia/reoxygenation (H-R). Furthermore, several different antioxidants are able to abrogate hepatocyte ROS-induced cell death during hypoxia and H-R. These data provide clear evidence that endogenous ROS production by mitochondria and nicotinamide adenine dinucleotide phosphate oxidase drives human hepatocyte apoptosis and necrosis during hypoxia and H-R and may therefore play an important role in any hepatic diseases characterized by a relatively hypoxic liver microenvironment. In conclusion, these data strongly suggest that hepatocytes and hepatocyte-derived ROS are active participants driving hepatic inflammation. These novel findings highlight important functional/metabolic differences between hepatocytes isolated from normal donor livers, hepatocytes isolated from normal resected tissue obtained during surgery for malignant neoplasms, and hepatocytes isolated from livers with end-stage disease. Furthermore, the targeting of hepatocyte ROS generation with antioxidants may offer therapeutic potential for the adjunctive treatment of IRI and chronic inflammatory liver diseases. |
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Authors:
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Ricky Harminder Bhogal; Stuart M Curbishley; Christopher J Weston; David H Adams; Simon C Afford |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Volume: 16 ISSN: 1527-6473 ISO Abbreviation: Liver Transpl. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100909185 Medline TA: Liver Transpl Country: United States |
Other Details:
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Languages: eng Pagination: 1303-13 Citation Subset: IM |
Copyright Information:
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© 2010 AASLD. |
Affiliation:
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Centre for Liver Research, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham, United Kingdom. balsin@hotmail.com |
Export Citation:
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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DDDP.RCHX14183//Wellcome Trust |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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