Detection of the enzymatic activity of cytochrome P-450 enzymes by high-performance liquid chromatography

Jansen, Eugène; Fluiter, Petra de

doi:10.1016/0378-4347(92)80541-w

Cited by 12 publications

(3 citation statements)

References 75 publications

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“…This is consistent with the decrease in CYP3A1, an isozyme that is responsible, in untreated rat, for the N-demethylation of benzphetamine and 16p hydroxylation of testosterone (54). On the other hand, the decrease of the activity of BzND agrees well with the decrease in the production of 2ahydroxytestosterone; both of them are related to CYP2C11 (55). In contrast, in hamsters, CF3 treatment increased the BzND and testosterone 16Phydroxylase activities.…”

Section: Discussionsupporting

confidence: 74%

Differential modulation of hepatic cytochrome P‐450 enzymes in rat and syrian hamster by 4′‐trifluoromethyl‐2,3,4,5‐tetrachlorobiphenyl

Bani

Narbonne

Fukuhara

et al. 1994

J. Biochem. Toxicol.

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The effects of a single injection (40 mg/kg) of 4'-trifluoromethyl-2,3,4,5-tetrachlorobiphenyl (CF3) on hepatic cytochrome P-450 monooxygenases were assessed in rat and syrian hamster. The CF3 treatment significantly increased the total amount of cytochrome P-450 in both species. In rats, CF3 treatment caused marked increases in ethoxyresorufin O-deethylase (EROD), arylhydrocarbon hydroxylase (AHH), and testosterone 7 alpha-hydroxylase activities but significantly reduced the activities of benzphetamine N-demethylase (BzND), erythromycin N-demethylase (ErND), testosterone 6 beta, 16 alpha, and 16 beta-hydroxylase, and formation of androstenedione. Administration of CF3 to hamsters strongly induced the activities of EROD, AHH, BzND, testosterone 15 alpha, and 16 alpha-hydroxylases, and androstenedione production, whereas ErND, testosterone 6 beta, and 7 alpha-hydroxylases were decreased. Administration of CF3 to rats induced the CYP1A family proteins and CYP2A1, while CF3 reduced the level of CYP2B1, and, to a lesser extent, of CYP6 beta 2. In hamsters, CF3 treatment significantly induced the CYP1A2, CYP2A1, CYP2A8, and CYP2B1 isozymes, whereas the CYP6 beta 2 level was decreased. The ability of hepatic microsomes to activate aflatoxin B1 and benzo(a)pyrene was elevated by CF3 treatment in hamsters, while activation of aflatoxin B1 was decreased in microsomes from CF3-treated rats. These results showed differences in the CF3-induced pattern of rat and hamster cytochrome P-450 monooxygenases.

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Section: Discussionsupporting

confidence: 74%

Differential modulation of hepatic cytochrome P‐450 enzymes in rat and syrian hamster by 4′‐trifluoromethyl‐2,3,4,5‐tetrachlorobiphenyl

Bani

Narbonne

Fukuhara

et al. 1994

J. Biochem. Toxicol.

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“…There are several approaches to dissect the complex pattern of CYP proteins in cells and tissues exploiting chromatographic, 8-12 spectroscopic 13,14 and enzymatic CYP properties. [15][16][17] Finally, specific antibodies can be used in combination with ELISA and Western-blotting. Proteomic techniques including 2D-gel electrophoresis and organic mass spectrometry were not so successful up to now and the reasons for this were discussed elsewhere.…”

Section: Introductionmentioning

confidence: 99%

Multi-parametric analysis of cytochrome P450 expression in rat liver microsomes by LA-ICP-MS

Waentig

Jakubowski

Roos

2011

J. Anal. At. Spectrom.

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Quantitative analysis of cytochrome P450 (CYP) patterns of cells and tissues is an important aspect in toxicological and pharmacological research as this group of enzymes is largely involved in the metabolism of toxic compounds and drugs. Here we present a method for the multi-parametric and simultaneous quantitative determination of several cytochromes P450 in liver microsomes of untreated and inducer treated rats. The method is based on the binding of specifically lanthanide labelled antibodies to electrophoretically separated and blotted CYP proteins and their subsequent identification and quantification by LA-ICP-MS. CYP1A1, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 were simultaneously quantified and the patterns between microsomal samples were compared. Microsomes of rats treated with 3-methylcholanthrene, phenobarbital and dexamethasone showed increased levels of CYP1A1, CYP2B1 and CYP3A1, respectively. These results coincide with data obtained by independent methods for CYP quantification, i.e. ethoxyresorufin O-deethylase activity for CYP1A1 and pentoxyresorufin O-depentylase for CYP2B1. The presented method is useful for multi-parametric CYP profiling and has further large potential with respect to the number of analysed parameters/proteins and sensitivity.

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“…It is well established that regio-and stereospecific hydroxylation of steroidal molecules provides a sensitive indicator for specific CYP isoenzymes (Wood et al 1983;Van der Hoeven 1984;Khatsenko et al 1990;Jansen & Fluiter 1992;Lee et al 2003) and the usefulness of androstendione as a substrate for rat liver microsomal studies has also been reported (Khatsenko et al 1990).…”

Section: Steroid Metabolism In Hepatic Microsomesmentioning

confidence: 99%

Influence of the Ginkgo extract EGb 761 on rat liver cytochrome P450 and steroid metabolism and excretion in rats and man

Chatterjee

Doelman

Nöldner

et al. 2005

Journal of Pharmacy and Pharmacology

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Extracts from leaves of Ginkgo biloba L. are among the most used herbal medicinal products worldwide. Based on in-vitro tests and studies in rats, concern has been expressed that intake of Ginkgo extracts may affect hepatic metabolism of xenobiotics and cause drug interactions, although no evidence for modulation of cytochrome P450 (CYP450) enzyme activity was obtained in human trials. Because of these contradictory findings, we investigated the effects of the standardised extract EGb 761 on hepatic CYP450 in rats. EGb 761 (100 mg kg-1 daily, p.o., for 4 days) strongly increased liver CYP450 content and altered the ex-vivo biotransformation of androstendione, as well as metabolism of endogenous steroids. However, in human subjects no effect on the urinary steroid profile was observed after intake of EGb 761 for 28 days (240 mg daily). These results indicate that the effects of EGb 761 on drug metabolising enzymes are specific for rats and may not be extrapolated to man.

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Detection of the enzymatic activity of cytochrome P-450 enzymes by high-performance liquid chromatography

Cited by 12 publications

References 75 publications

Differential modulation of hepatic cytochrome P‐450 enzymes in rat and syrian hamster by 4′‐trifluoromethyl‐2,3,4,5‐tetrachlorobiphenyl

Differential modulation of hepatic cytochrome P‐450 enzymes in rat and syrian hamster by 4′‐trifluoromethyl‐2,3,4,5‐tetrachlorobiphenyl

Multi-parametric analysis of cytochrome P450 expression in rat liver microsomes by LA-ICP-MS

Influence of the Ginkgo extract EGb 761 on rat liver cytochrome P450 and steroid metabolism and excretion in rats and man

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