| Effects of long-term ethanol administration in a rat total enteral nutrition model of alcoholic liver disease. | |
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MedLine Citation:
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PMID: 21051528 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Male Sprague-Dawley rats were chronically fed a high-unsaturated-fat diet for 130 days by using total enteral nutrition (TEN), or the same diet in which ethanol (EtOH) isocalorically replaced carbohydrate calories. Additional groups were supplemented with the antioxidant N-acetylcysteine (NAC) at 1.7 g·kg(-1)·day(-1). Relative to an ad libitum chow-fed group, the high-fat-fed controls had three- to fourfold greater expression of fatty acid transporter CD36 mRNA and developed mild steatosis but little other hepatic pathology. NAC treatment resulted in increased somatic growth relative to controls (4.0 ± 0.1 vs. 3.1 ± 0.1 g/day) and increased hepatic steatosis score (3.5 ± 0.6 vs. 2.7 ± 1.2), associated with suppression of the triglyceride hydrolyzing protein adiponutrin, but produced no elevation in serum alanine aminotransferase (ALT). Chronic EtOH treatment increased expression of fatty acid transport protein FATP-2 mRNA twofold, resulting in marked hepatic steatosis, oxidative stress, and a twofold elevation in serum ALT. However, no changes in tumor necrosis factor-α or transforming growth factor-β expression were observed. Fibrosis, as measured by Masson's trichrome and picrosirius red staining, and a twofold increase in expression of type I and type III collagen mRNA, was only observed after EtOH treatment. Long-term EtOH treatment increased hepatocyte proliferation but did not modify the hepatic mRNAs for hedgehog pathway ligands or target genes or genes regulating epithelial-to-mesenchymal transition. Although the effects of NAC on EtOH-induced fibrosis could not be fully evaluated, NAC had additive effects on hepatocyte proliferation and prevented EtOH-induced oxidative stress and necrosis, despite a failure to reverse hepatic steatosis. |
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Authors:
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Martin J J Ronis; Leah Hennings; Ben Stewart; Alexei G Basnakian; Eugene O Apostolov; Emanuele Albano; Thomas M Badger; Dennis R Petersen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-04 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 300 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-30 Completed Date: 2011-02-01 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G109-19 Citation Subset: IM |
Affiliation:
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epartment of Pharmacology and Toxicology, 2University of Arkansas for Medical Sciences and Arkansas Children's Nutrition Center, Little Rock, Arkansas 72202, USA. RonisMartinJ@uams.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology,
therapeutic use Animals Cell Proliferation / drug effects Cytochrome P-450 Enzyme System / metabolism Dietary Fats / administration & dosage Enteral Nutrition Ethanol / pharmacology, toxicity* Fatty Liver / etiology*, pathology Hedgehog Proteins / metabolism Lipid Metabolism / drug effects Liver / drug effects*, pathology Liver Diseases, Alcoholic / metabolism*, pathology Liver Regeneration / drug effects Male Oxidative Stress / drug effects Rats |
| Grant Support | |
ID/Acronym/Agency:
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R01 AA009300/AA/NIAAA NIH HHS; R01 AA08645/AA/NIAAA NIH HHS; R01 AA18282/AA/NIAAA NIH HHS; R01 DK078908/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Hedgehog Proteins; 616-91-1/Acetylcysteine; 64-17-5/Ethanol; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Cyp2f2 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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