A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers

Low Teck Yew, Kar Leow Chon, Manuel Salto-Tellez, Maxey C.M. Chung

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Thioacetamide (TAA) administration is an established technique for generating rat models of liver fibrosis and cirrhosis. Oxidative stress is believed to be involved as TAA-induced liver fibrosis is initiated by thioacetamide S-oxide, which is derived from the biotransformation of TAA by the microsomal flavine-adenine dinucleotide (FAD)-containing monooxygense (FMO) and cytochrome P450 systems. A two-dimensional gel electrophoresis-mass spectrometry approach was applied to analyze the protein profiles of livers of rats administered with sublethal doses of TAA for 3, 6 and 10 weeks respectively. With this approach, 59 protein spots whose expression levels changed significantly upon TAA administration were identified, including three novel proteins. These proteins were then sorted according to their common biochemical properties and functions, so that pathways involved in the pathogenesis of rat liver fibrosis due to TAA-induced toxicity could be elucidated. As a result, it was found that TAA-administration down-regulated the enzymes of the primary metabolic pathways such as fatty acid β-oxidation, branched chain amino acids and methionine breakdown. This phenomenon is suggestive of the depletion of succinyl-CoA which affects heme and iron metabolism. Up-regulated proteins, on the other hand, are related to oxidative stress and lipid peroxidation. Finally, these proteomics data and the data obtained from the scientific literature were integrated into an "overview model" for TAA-induced liver cirrhosis. This model could now serve as a useful resource for researchers working in the same area.

Original languageEnglish
Pages (from-to)3960-3974
Number of pages15
JournalProteomics
Volume4
Issue number12
DOIs
Publication statusPublished - 1 Dec 2004
Externally publishedYes

Fingerprint

Thioacetamide
Liver
Proteomics
Rats
Fibrosis
Liver Cirrhosis
Oxidative stress
Proteins
Oxidative Stress
Literature
Branched Chain Amino Acids
Electrophoresis, Gel, Two-Dimensional
Adenine
Biotransformation
Metabolic Networks and Pathways
Electrophoresis
Heme
Metabolism
Methionine
Cytochrome P-450 Enzyme System

Keywords

  • Liver fibrosis and cirrhosis
  • Matrix-assisted laser desorption/ionization- time of flight mass spectrometry
  • Thioacetamide
  • Two-dimensional gel electrophoresis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers. / Teck Yew, Low; Chon, Kar Leow; Salto-Tellez, Manuel; Chung, Maxey C.M.

In: Proteomics, Vol. 4, No. 12, 01.12.2004, p. 3960-3974.

Research output: Contribution to journalArticle

Teck Yew, Low ; Chon, Kar Leow ; Salto-Tellez, Manuel ; Chung, Maxey C.M. / A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers. In: Proteomics. 2004 ; Vol. 4, No. 12. pp. 3960-3974.
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