Volume 26, Issue 11 p. 1726-1730
Research Article

Modulation of Hepatic Drug Metabolizing Enzymes by Dietary Doses of Thymoquinone in Female New Zealand White Rabbits

Fawzy Elbarbry

Fawzy Elbarbry

School of Pharmacy, Pacific University Oregon, Hillsboro, OR, 97123 USA

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Ahmed Ragheb

Ahmed Ragheb

Department of General Medicine, College of Medicine, Menofyia University, Egypt

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Travis Marfleet

Travis Marfleet

Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada

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Ahmed Shoker

Corresponding Author

Ahmed Shoker

Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada

Dr Ahmed Shoker, Director of Transplant Program, Department of Medicine, Division of Nephrology, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK, Canada S7N 0 W8.

E-mail: [email protected]

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First published: 15 March 2012
Citations: 24

Abstract

Herbal medicines can affect drug metabolizing enzymes. Therefore the effect of thymoquinone (TQ), the active ingredient of black seeds, was examined on rabbit liver drug metabolizing enzymes. Two groups of New Zealand female rabbits received TQ at 10 and 20 mg/kg/day orally and a control group of six animals each were killed after 8 weeks. Blood and livers were harvested and the activity of cytochrome P450 (CYP) and phase II enzymes in the microsomal and cytosolic preparations were measured by HPLC and ELISA methods. The liver enzymes ALT/AST and albumin were similar in the three groups. CYP1A2, CYP3A4, but not CYP2E1, were significantly diminished by TQ treatment. Of the phase II enzymes, glutathione-S-transferase (GST) and glutathione peroxidase (GPx) were significantly induced by the high TQ dose, while the total glutathione levels were unaffected. Glutathione reductase (GR), on the other hand, was significantly induced in the two experimental groups. Thymoquinone has differential effects on CYP and phase II enzymes. Inhibition of some CYP enzyme activities may lead to a hazardous herb–drug interaction. Induction of GR activity may explain the salutatory effect of the black seeds in inhibiting the generation of bioactive metabolites known to promote carcinogenesis and oxidative cell damage. Copyright © 2012 John Wiley & Sons, Ltd.

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