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Oxidative stress is believed to be involved as TAA\u2010induced liver fibrosis is initiated by thioacetamide <jats:italic>S<\/jats:italic>\u2010oxide, which is derived from the biotransformation of TAA by the microsomal flavine\u2010adenine dinucleotide (FAD)\u2010containing monooxygense (FMO) and cytochrome P450 systems. A two\u2010dimensional gel electrophoresis\u2010mass 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\u2010induced toxicity could be elucidated. As a result, it was found that TAA\u2010administration down\u2010regulated the enzymes of the primary metabolic pathways such as fatty acid \u03b2\u2010oxidation, branched chain amino acids and methionine breakdown. This phenomenon is suggestive of the depletion of succinyl\u2010CoA which affects heme and iron metabolism. Up\u2010regulated 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 \u201coverview model\u201d for TAA\u2010induced liver cirrhosis. This model could now serve as a useful resource for researchers working in the same area.<\/jats:p>","DOI":"10.1002\/pmic.200400852","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T06:51:53Z","timestamp":1100242313000},"page":"3960-3974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":128,"title":["A proteomic analysis of thioacetamide\u2010induced hepatotoxicity and cirrhosis in rat livers"],"prefix":"10.1002","volume":"4","author":[{"given":"Teck Yew","family":"Low","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chon Kar","family":"Leow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Salto\u2010Tellez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxey C. 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