| Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis. | |
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MedLine Citation:
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PMID: 1639354 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The precise role of lipid peroxidation in the pathogenesis of alcoholic liver disease is still being debated. To explore the issue, this study was undertaken to investigate the status of lipid peroxidation, antioxidants and prooxidants at two discrete stages of experimental alcoholic liver disease. Male Wistar rats were intragastrically fed a high-fat diet plus ethanol for 5 or 16 wk (the duration that resulted in initiation of centrilobular liver necrosis or liver fibrosis, respectively). Lipid peroxidation was assessed in isolated microsomes and mitochondria with three parameters: malondialdehyde equivalents as determined by thiobarbituric acid assay, conjugated diene formation and 4-hydroxynonenal as a 2,4-dinitrophenylhydrazone derivative. To assess antioxidant systems, hepatic concentrations of glutathione, methionine and alpha-tocopherol were determined. The concentration of nonheme iron, a known prooxidant, was also measured. At wk 5, centrilobular liver necrosis was already evident in the ethanol-fed animals, with two- or threefold increases in plasma AST and ALT levels. At this stage, neither malondialdehyde equivalents nor conjugated diene values were elevated, and the 4-hydroxynonemal level was below 0.2 nmol/mg protein. Hepatic concentrations of methionine and alpha-tocopherol in these animals were increased two- and threefold, respectively, whereas the reduced glutathione level remained unchanged. When alcoholic liver disease had progressed to perivenular or bridging fibrosis at wk 16, all three parameters of lipid peroxidation showed consistent increases that were accompanied by significant reductions in the hepatic glutathione and methionine levels. Interestingly, the control animals pair-fed with the high-fat diet also had significantly elevated 4-hydroxynonenal levels at wk 16 compared to the wk 5 level.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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S Kamimura; K Gaal; R S Britton; B R Bacon; G Triadafilopoulos; H Tsukamoto |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 16 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 1992 Aug |
Date Detail:
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Created Date: 1992-09-02 Completed Date: 1992-09-02 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 448-53 Citation Subset: IM |
Affiliation:
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Department of Medicine, Veterans Affairs Medical Center, Martinez, California 94553. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldehydes
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analysis* Animals Lipid Peroxidation* Liver / chemistry*, pathology Liver Cirrhosis, Alcoholic / etiology, metabolism* Male Rats Rats, Inbred Strains |
| Grant Support | |
ID/Acronym/Agency:
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AA06603/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aldehydes; 29343-52-0/4-hydroxy-2-nonenal |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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