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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 12/2012

01-12-2012 | Original Article

Hepatic Injury Due to Combined Choline-Deprivation and Thioacetamide Administration: An Experimental Approach to Liver Diseases

Authors: Hussam Al-Humadi, Stamatios Theocharis, Ismene Dontas, Vasileios Stolakis, Apostolos Zarros, Argyro Kyriakaki, Rafal Al-Saigh, Charis Liapi

Published in: Digestive Diseases and Sciences | Issue 12/2012

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Abstract

Background

The induction of prolonged choline-deprivation (CD) in rats receiving thioacetamide (TAA) is an experimental approach of mild hepatotoxicity that could resemble commonly presented cases in clinical practice (in which states of malnutrition and/or alcoholism are complicated by the development of other liver-associated diseases).

Aim

The present study aimed to investigate the time-dependent effects of a 30-, a 60- and a 90-day dietary CD and/or TAA administration on the adult rat liver histopathology and the serum markers of hepatic functional integrity.

Methods

Rats were divided into four main groups: (a) control, (b) CD, (c) TAA and (d) CD + TAA. Dietary CD was provoked through the administration of choline-deficient diet, while TAA administration was performed ad libitum through the drinking water (300 mg/l of drinking water).

Results

Histological examination of the CD + TAA liver sections revealed micro- and macro-vesicular steatosis with degeneration and primary fibrosis at day 30, to extensive steatosis and fibrosis at day 90. Steatosis was mostly of the macrovesicular type, involving all zones of the lobule, while inflammatory infiltrate consisted of foci of acute and chronic inflammatory cells randomly distributed in the lobule. These changes were accompanied by gradually increasing mitotic activity, as well as by a constantly high alpha-smooth muscle actin immunohistochemical staining. The determination of hepatocellular injury markers such as the serum enzyme levels’ of alanine aminotransferase and aspartate aminotransferase demonstrated a decrease at day 30 (they returned to control levels at days 60 and 90). However, the determination of those serum enzymes used for the assessment of cholestatic liver injury (gamma-glutamyltransferase, alkaline phosphatase) revealed a constant (time-independent) statistically-significant increase versus control values.

Conclusions

Long-term combined dietary CD and TAA administration could be a more realistic experimental approach to human liver diseases involving severe steatosis, fibrosis, stellate cell activation and significant regenerative hepatocellular response.
Footnotes
1
Ingredients of the CDD: sucrose, coconut oil, starch wheat, dextrine, extracted peanut meal, soy protein, corn oil, dicalcium phosphate, cellulose, potassium citrate, sodium chloride, magnesium oxide, l-cystine, vitamin A, vitamin D3, vitamin E (alpha-tocopherol), copper (copper sulfate pentahydrate), selenium (sodium selenite). Analysis: protein (12 %), fat (16 %), fiber (2 %), ash (3.5 %).
 
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Metadata
Title
Hepatic Injury Due to Combined Choline-Deprivation and Thioacetamide Administration: An Experimental Approach to Liver Diseases
Authors
Hussam Al-Humadi
Stamatios Theocharis
Ismene Dontas
Vasileios Stolakis
Apostolos Zarros
Argyro Kyriakaki
Rafal Al-Saigh
Charis Liapi
Publication date
01-12-2012
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 12/2012
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-012-2299-9

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