Nicotine Metabolism in Liver Microsomes from Rats with Acute Hepatitis or Cirrhosis

作者: Yoshihiko Funae , Yukio Kuroiwa , Takemi Yoshida , Toshinori Yamamoto , Kanae Iwata

DOI:

关键词:

摘要: Nicotine exerts a number of physiological effects. is absorbed through the lungs with smoking and rapidly metabolized in humans. Although it mainly liver, effects liver injuries on nicotine metabolism are not clear. The purpose this study was to clarify metabolism. Rats were treated D-galactosamine (GalN) or thioacetamide (TA), induce acute hepatitis cirrhosis, respectively. Serum transaminase levels significantly elevated model rats both types injury. Cytochrome P450 (CYP) cytochrome b 5 contents microsomes decreased TA-treated cirrhotic but GalN-treated hepatitic rats. major metabolic pathways nicotine, i.e. cotinine formation catalyzed by CYP nicotine-1′- N -oxide flavin-containing monooxygenase, investigated these rat microsomes. Formation from changed rats, comparison controls, By immunoblotting, decreases CYP1A2, CYP2B2, CYP2C, CYP2E1 protein recognized It also shown that maximal velocity values for decreased, compared controls. These results suggested reduction cirrhosis due monooxygenase expression levels.

参考文章(42)
G. Paintaud, M.-P. Brientini, Y. Bechtel, J.-P. Miguet, P. R. Bechtel, Effects of liver diseases on drug metabolism Therapie. ,vol. 51, pp. 384- 389 ,(1996)
Alvah H. Phillips, Robert G. Langdon, Hepatic Triphosphopyridine Nucleotide-Cytochrome c Reductase: Isolation, Characterization, and Kinetic Studies Journal of Biological Chemistry. ,vol. 237, pp. 2652- 2660 ,(1962) , 10.1016/S0021-9258(19)73803-4
Tsuneo Omura, Ryo Sato, The Carbon Monoxide-binding Pigment of Liver Microsomes Journal of Biological Chemistry. ,vol. 239, pp. 2379- 2385 ,(1964) , 10.1016/S0021-9258(20)82245-5
Diseases of the liver and biliary system (11th ed.). Blackwell Science (2002). ,(2001) , 10.1002/9780470986820
K Chatamra, E Proctor, Controlled induction of cirrhosis in the rat. British journal of experimental pathology. ,vol. 64, pp. 320- 330 ,(1983)
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
K.-I. Nunoya, Y. Funae, Y. Kuroiwa, T. Yokoi, K. Nagashima, T. Yamamoto, T. Kamataki, K. Inoue, N. Shimada, M. Nakajima, Role of human cytochrome P4502A6 in C-oxidation of nicotine. Drug Metabolism and Disposition. ,vol. 24, pp. 1212- 1217 ,(1996)
Neal L. Benowitz, Peyton Jacob, Metabolism, Pharmacokinetics and Pharmacodynamics of Nicotine in Man Tobacco Smoking and Nicotine. pp. 357- 373 ,(1987) , 10.1007/978-1-4613-1911-5_23