Cytochrome P-450 CYP1A2

Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Ginseng extract has been reported to decrease the incidence of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated tumorigenesis in mice. A potential mechanism for this effect by ginseng is inhibition of DMBA-bioactivating cytochrome P450 (P450) enzymes. In the present in vitro study, we examined the effect of a standardized Panax ginseng (or Asian ginseng) extract (G115), a standardized Panax quinquefolius (or North American ginseng) extract (NAGE), and individual ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) on CYP1 catalytic activities, as assessed by 7-ethoxyresorufin O-dealkylation.

Author(s): 
Chang, Thomas K. H.
Chen, Jie
Benetton, Salete A.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Treatment of rats with a single oral dose (10-30 mg/kg) of a crude Panax ginseng extract of unknown ginsenoside content has been reported to modestly increase hepatic microsomal cytochrome P450-mediated aminopyrine N-demethylation activity. In the present study, we compared the effect of P. ginseng and Panax quinquefolius extracts on rat hepatic CYP2B1, CYP3A23, and CYP1A2 gene expression. Adult male Sprague-Dawley rats (250-275 g) received, by oral gavage or i.p., P. ginseng extract [4% (w/w) total ginsenosides; 30 or 100 mg/kg/day for 1 or 4 days], P.

Author(s): 
Yu, Chia-Ting
Chen, Jie
Teng, Xiao Wei
Tong, Vincent
Chang, Thomas K. H.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

The female flowers of hops (Humulus lupulus L.) are used in the brewing of beer and are under investigation for use in dietary supplements for the management of menopausal symptoms in women. Hop extracts contain the weakly estrogenic compound isoxanthohumol (IX), proestrogenic xanthohumol, and the potent estrogen 8-prenylnaringenin (8PN). Because IX can be metabolized in the human liver to form 8PN, the specific cytochrome P450 (P450) enzymes responsible for this O-demethylation reaction were identified.

Author(s): 
Guo, Jian
Nikolic, Dejan
Chadwick, Lucas R.
Pauli, Guido F.
van Breemen, Richard B.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

CYP2E1 is widely accepted as the sole form of cytochrome P450 responsible for alcohol-mediated increases in acetaminophen (APAP) hepatotoxicity. However, we previously found that alcohol [ethanol and isopentanol (EIP)] causes increases in APAP hepatotoxicity in Cyp2e1(-/-) mice, indicating that CYP2E1 is not essential. Here, using wild-type and Cyp2e1(-/-) mice, we investigated the relative roles of CYP2E1 and CYP3A in EIP-mediated increases in APAP hepatotoxicity.

Author(s): 
Wolf, Kristina K.
Wood, Sheryl G.
Allard, Jenna L.
Hunt, Jane A.
Gorman, Nadia
Walton-Strong, Brooke W.
Szakacs, Juliana G.
Duan, Su X.
Hao, Qin
Court, Michael H.
von Moltke, Lisa L.
Greenblatt, David J.
Kostrubsky, Vsevolod
Jeffery, Elizabeth H.
Wrighton, Steven A.
Gonzalez, Frank J.
Sinclair, Peter R.
Sinclair, Jacqueline F.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Members of the cytochrome P450 (P450) enzyme families CYP1, CYP2, and CYP3 are responsible for the metabolism of approximately 75% of all clinically relevant drugs. With the increased prevalence of nonalcoholic fatty liver disease (NAFLD), it is likely that patients with this disease represent an emerging population at significant risk for alterations in these important drug-metabolizing enzymes. The purpose of this study was to determine whether three progressive stages of human NALFD alter hepatic P450 expression and activity.

Author(s): 
Fisher, Craig D.
Lickteig, Andrew J.
Augustine, Lisa M.
Ranger-Moore, James
Jackson, Jonathan P.
Ferguson, Stephen S.
Cherrington, Nathan J.
Publication Title: 
British Journal of Pharmacology

BACKGROUND AND PURPOSE: Hyperbilirubinaemia and cholestasis are two major forms of liver abnormality. The Chinese herb Yin Chin has been used for thousands of years to treat liver dysfunctions. In mice, this herb and its principal ingredient scoparone were found to accelerate the clearance of bilirubin accompanied by the induction of uridine diphosphate-5'-glucuronosyltransferase-1A1 (UGT1A1), a bilirubin processing enzyme. The aim of this study was to determine whether scoparone induces the expression of human UGT1A1.

Author(s): 
Yang, Dongfang
Yang, Jian
Shi, Deshi
Deng, Ruitang
Yan, Bingfang
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Rutaecarpine, evodiamine, and dehydroevodiamine are quinazolinocarboline alkaloids isolated from a traditional Chinese medicine, Evodia rutaecarpa. The in vitro effects of these alkaloids on cytochrome P450 (P450)-catalyzed oxidations were studied using mouse and human liver microsomes. Among these alkaloids, rutaecarpine showed the most potent and selective inhibitory effect on CYP1A-catalyzed 7-methoxyresorufin O-demethylation (MROD) and 7-ethoxyresorufin O-deethylation (EROD) activities in untreated mouse liver microsomes. The IC(50) ratio of EROD to MROD was 6.

Author(s): 
Ueng, Yune-Fang
Jan, Woan-Ching
Lin, Lie-Chwen
Chen, Ta-Liang
Guengerich, F. Peter
Chen, Chieh-Fu
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