Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases

PLoS One. 2015 Jun 1;10(6):e0128253. doi: 10.1371/journal.pone.0128253. eCollection 2015.

Abstract

Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Animals
  • Disease Models, Animal
  • Feasibility Studies
  • Gene Expression Regulation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver / physiopathology
  • Liver Diseases, Alcoholic* / etiology
  • Liver Diseases, Alcoholic* / metabolism
  • Liver Diseases, Alcoholic* / pathology
  • Liver Diseases, Alcoholic* / physiopathology
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Tupaiidae*

Substances

  • NF-E2-Related Factor 2

Grant support

This work was supported in part by the Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases (2013A061401013), Special Fund for Agro-scientific Research in the Public Interest (201303042) and Natural Science Foundation of Guangdong Province (S2013040016474).