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 beta-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.