Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nicotine exerts a number of physiological effects. Nicotine is absorbed through the lungs with smoking and is rapidly metabolized in humans. Although it is mainly metabolized in the liver, the effects of liver injuries on nicotine metabolism are not clear. The purpose of this study was to clarify the effects of liver injuries on nicotine metabolism. Rats were treated with D-galactosamine (GalN) or thioacetamide (TA), to induce acute hepatitis or liver cirrhosis, respectively. Serum transaminase levels were significantly elevated in model rats with both types of liver injury. Cytochrome P450 (CYP) and cytochrome b5 contents in liver microsomes were decreased significantly in TA-treated cirrhotic rats but not in GalN-treated hepatitic rats. The major metabolic pathways of nicotine, i.e. cotinine formation catalyzed by CYP and nicotine-1'-N-oxide formation catalyzed by flavin-containing monooxygenase, were investigated in these rat liver microsomes. Formation of cotinine and nicotine-1'-N-oxide from nicotine was not changed in GalN-treated hepatitic rats, in comparison with the controls, but was significantly decreased in TA-treated cirrhotic rats. By immunoblotting, decreases in CYP1A2, CYP2B2, CYP2C, and CYP2E1 protein were recognized in liver microsomes from TA-treated cirrhotic rats. It was also shown that the maximal velocity values for nicotine-1'-N-oxide formation in TA-treated cirrhotic rats were significantly decreased, compared with the controls. These results suggested that the reduction of nicotine metabolism in cirrhosis was due to decreases in CYP and flavin-containing monooxygenase protein expression levels.
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PMID:Nicotine metabolism in liver microsomes from rats with acute hepatitis or cirrhosis. 944 50

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.
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PMID:A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers. 1552 43