Cytochrome P-450 CYP1A1

Publication Title: 
Tropical medicine & international health: TM & IH

Amodiaquine (AQ) is a 4-aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short-lived quinine-imine.

Author(s): 
Cavaco, I.
Piedade, R.
Msellem, M. I.
Bjorkman, A.
Gil, J. P.
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: 
Anticancer Research

BACKGROUND: Previous studies indicate that specific extracts and the pure triterpene glycoside actein obtained from black cohosh inhibit growth of human breast cancer cells. Our aim is to identify alterations in gene expression induced by treatment with a methanolic extract (MeOH) of black cohosh. MATERIALS AND METHODS: We treated MDA-MB-453 human breast cancer cells with the MeOH extract at 40 microg/ml and collected RNA at 6 and 24 h; we confirmed the microarray results with real-time RT-PCR for 18 genes.

Author(s): 
Einbond, Linda Saxe
Su, Tao
Wu, Hsan-au
Friedman, Richard
Wang, Xiaomei
Jiang, Bei
Hagan, Timothy
Kennelly, Edward J.
Kronenberg, Fredi
Weinstein, I. Bernard
Publication Title: 
The Journal of Steroid Biochemistry and Molecular Biology

Estrogen exposure and metabolism may play an important role in the development of estrogen-sensitive cancers in postmenopausal women. In this study we investigated whether past oral contraceptive (OC) administration or current dietary isoflavonoids (IF) affected expression and/or activity of steroid hormone-metabolizing cytochrome P450 (CYP) enzymes using complementary primate and cell culture models.

Author(s): 
Scott, L. M.
Durant, P.
Leone-Kabler, S.
Wood, C. E.
Register, T. C.
Townsend, A.
Cline, J. M.
Publication Title: 
Molecular Nutrition & Food Research

SCOPE: The "fetal basis of adult disease" hypothesis proposes that prenatal exposure to environmental stress can lead to increased susceptibility to clinical disorders later in life. In utero exposure of fetus to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to alterations in T-cell differentiation in the thymus and increased susceptibility to autoimmune disease later in life. TCDD triggers toxicity through activation of aryl hydrocarbon receptor and severely affects maternal and fetal immune system during pregnancy.

Author(s): 
Singh, Narendra P.
Singh, Ugra S.
Nagarkatti, Mitzi
Nagarkatti, Prakash S.
Publication Title: 
PloS One

BACKGROUND: MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation.

Author(s): 
Singh, Narendra P.
Singh, Udai P.
Guan, Hongbing
Nagarkatti, Prakash
Nagarkatti, Mitzi
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
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

β-Naphthoflavone (BNF) is a synthetic flavone that selectively and potently induces CYP1A enzymes via aryl hydrocarbon receptor activation. Mechanism-based mathematical models of CYP1A enzyme induction were developed to predict the time course of enzyme induction and quantitatively evaluate the interrelationship between BNF plasma concentrations, hepatic CYP1A1 and CYP1A2 mRNA levels, and CYP1A enzyme activity in rats in vivo. Male Sprague-Dawley rats received a continuous intravenous infusion of vehicle or 1.5 or 6 mg · kg(-1) · h(-1) BNF for 6 h, with blood and liver sampling.

Author(s): 
Chen, Emile P.
Chen, Liangfu
Ji, Yan
Tai, Guoying
Wen, Yuan H.
Ellens, Harma
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