Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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