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Authors

Lynell W. Klassen, Experimental Immunology Laboratory at the University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology, 983025 Nebraska Medical Center, Omaha, NE 68198-3025, United States
Geoffrey M. Thiele, Experimental Immunology Laboratory at the University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology, 983025 Nebraska Medical Center, Omaha, NE 68198-3025, United States
Michael J. Duryee, Experimental Immunology Laboratory at the University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology, 983025 Nebraska Medical Center, Omaha, NE 68198-3025, United States
Courtney S. Schaffert, Experimental Immunology Laboratory at the Omaha Veterans Administration Medical Center, Research Services 151, 4101 Woolworth Avenue, Omaha, NE 68105, United States
Amy L. DeVeney, Experimental Immunology Laboratory at the University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology, 983025 Nebraska Medical Center, Omaha, NE 68198-3025, United States
Carlos D. Hunter, Experimental Immunology Laboratory at the University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology, 983025 Nebraska Medical Center, Omaha, NE 68198-3025, United States
Peter Olinga, University of Groningen, GUIDE, Department of Pharmacokinetics & Drug Delivery, Ant.Deusinglaan 1, 9713 AV Groningen, The Netherlands
Dean J. Tuma, Experimental Immunology Laboratory at the Omaha Veterans Administration Medical Center, Research Services 151, 4101 Woolworth Avenue, Omaha, NE 68105, United States

Date of this Version

2008

Comments

Published in Biochemical Pharmacology 76 (2008) 426 – 436.

Abstract

Alcohol abuse results in liver injury, but investigations into the mechanism(s) for this injury have been hampered by the lack of appropriate in vitro culture models in which to conduct in depth and specific studies. In order to overcome these shortcomings, we have developed the use of precision-cut liver slices (PCLS) as an in vitro culture model in which to investigate how ethanol causes alcohol-induced liver injury. In these studies, it was shown that the PCLS retained excellent viability as determined by lactate dehydrogenase and adenosine triphosphate (ATP) levels over a 96-h period of incubation. More importantly, the major enzymes of ethanol detoxification; alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P4502E1, remained active and PCLS readily metabolized ethanol and produced acetaldehyde. Within 24 h and continuing up to 96 h the PCLS developed fatty livers and demonstrated an increase in the redox state. These PCLS secreted albumin, and albumin secretion was decreased by ethanol treatment. All of these impairments were reversed following the addition of 4-methylpyrazole, which is an inhibitor of ethanol metabolism. Therefore, this model system appears to mimic the ethanol-induced changes in the liver that have been previously reported in human and animal studies, and may be a useful model for the study of alcoholic liver disease.

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