Microarray gene analysis of the liver in a rat model of chronic, voluntary alcohol intake

Deaciuc, Ion V.; Peng, Xuejun; D'Souza, Nympha B.; Shedlofsky, Steven I.; Burikhanov, Ravshan; Voskresensky, Igor V.; de Villiers, Willem J.S.

doi:10.1016/j.alcohol.2003.12.001

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Volume 32, Issue 2 , Pages 113-127, February 2004

Microarray gene analysis of the liver in a rat model of chronic, voluntary alcohol intake

Ion V. Deaciuc
- College of Medicine, Department of Internal Medicine, Division of Digestive Diseases and Nutrition, 800 Rose Street, MN649A-0298, University of Kentucky, Lexington, KY 40536, USA
- Corresponding author and present address. School of Medicine, Department of Medicine, Division of Gastroenterology/Hepatology, 550 South Jackson Street, University of Louisville, Louisville, KY 40202, USA. Tel.: +1-502-852-3873; fax: +1-502-852-0846.
Xuejun Peng
- Cleveland Clinic Foundation, Department of Biostatistics and Epidemiology, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Nympha B. D'Souza
- College of Medicine, Department of Internal Medicine, Division of Pulmonary Critical Care, 800 Rose Street, MN649A-0298, University of Kentucky, Lexington, KY 40536, USA
Steven I. Shedlofsky
- College of Medicine, Department of Internal Medicine, Division of Digestive Diseases and Nutrition, 800 Rose Street, MN649A-0298, University of Kentucky, Lexington, KY 40536, USA
Ravshan Burikhanov
- College of Medicine, Department of Internal Medicine, Division of Digestive Diseases and Nutrition, 800 Rose Street, MN649A-0298, University of Kentucky, Lexington, KY 40536, USA
Igor V. Voskresensky
- College of Medicine, Department of Internal Medicine, Division of Digestive Diseases and Nutrition, 800 Rose Street, MN649A-0298, University of Kentucky, Lexington, KY 40536, USA
Willem J.S. de Villiers
- College of Medicine, Department of Internal Medicine, Division of Digestive Diseases and Nutrition, 800 Rose Street, MN649A-0298, University of Kentucky, Lexington, KY 40536, USA

Received 28 February 2003; received in revised form 4 December 2003; accepted 11 December 2003.

Editor: T.R. Jerrells

Abstract

The mechanisms underlying alcoholic liver disease are not fully understood. It has been established that alcohol interferes with transcriptional and translational regulatory steps of cell function. To understand such an effect, assessment of alcohol-induced changes in the simultaneous expression of a large number of genes may prove very useful. The purpose of the current study was to test a large number of genes (∼8,700) for possible changes in expression induced by alcohol alone or in addition to treatment with lipopolysaccharide (LPS), a putative mediator of alcohol effects on the liver. Male rats were fed an alcohol-containing liquid diet (Lieber–DeCarli) for 14–15 weeks, injected with Escherichia coli LPS (0.8 mg·kg⁻¹), and killed 24 h later. Blood samples were taken for determination of plasma liver enzyme activity, and liver samples were obtained for histologic evaluation and total RNA extraction. Total RNA was analyzed for gene expression (Rat Toxicology U34 Array; Affymetrix, Santa Clara, CA). Of 8,740 genes on the microchip, 2,259 were expressed in the liver. Seven hundred ninety-eight genes underwent significant changes induced by either alcohol or LPS, but listed in this article are only those that significantly increased or decreased expression twofold or more. The genes were assigned to functional groups and reviewed. Gene changes were discussed from two viewpoints: relevance to established hypotheses of alcohol and LPS mechanisms of action and revealing of novel mechanisms of alcohol-induced liver injury. Application of DNA microarray technology to the study of alcohol-induced liver injury generated novel theoretical and experimental approaches to alcohol-induced liver injury.

Keywords: DNA microarray, Gene expression, Lipopolysaccharide