The time-dependent effects of St John’s wort on cytochrome P450, uridine diphosphate-glucuronosyltransferase, glutathione S-transferase, and NAD(P)H-quinone oxidoreductase in mice
Autor: | Chiung-Chiao Huang, Yune-Fang Ueng, Yue-Rong Liu, Jin-Fu Yang |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Glucuronosyltransferase CYP3A lcsh:TX341-641 cytochrome P450 3A Pharmacology Kidney 03 medical and health sciences chemistry.chemical_compound Mice Cytochrome P-450 Enzyme System Hypericum perforatum NAD(P)H Dehydrogenase (Quinone) Animals Cytochrome P-450 CYP3A Drug Interactions Glutathione Transferase biology Dose-Response Relationship Drug Plant Extracts lcsh:RM1-950 Cytochrome P450 Glutathione CYP2E1 NAD cytochrome P450 2C Enzyme Activation Uridine diphosphate lcsh:Therapeutics. Pharmacology 030104 developmental biology Glutathione S-transferase chemistry Liver biology.protein Microsomes Liver lcsh:Nutrition. Foods and food supply Hypericum Food Science |
Zdroj: | Journal of Food and Drug Analysis, Vol 26, Iss 1, Pp 422-431 (2018) |
ISSN: | 1021-9498 |
DOI: | 10.1016/j.jfda.2017.01.004 |
Popis: | Hypericum perforatum [St. John’s wort (SJW)] is known to cause a drug interaction with the substrates of cytochrome P450 (P450, CYP) isoforms, mainly CYP3A. This study aims to determine the dose response and time course of the effects of SJW extract on P450s, UDP-glucuronosyltransferase (UGT), glutathione S-transferase (GST), and NAD(P)H-quinone oxidoreductase (NQO) in mice. The oral administration of SJW extract to male mice at 0.6 g/kg/d for 21 days increased hepatic oxidation activity toward a Cyp3a substrate nifedipine. By extending the SJW treatment to 28 days, hepatic nifedipine oxidation (NFO) and warfarin 7-hydroxylation (WOH) (Cyp2c) activities were increased by 95% and 34%, respectively. Immunoblot analysis of liver microsomal proteins revealed that the Cyp2c protein level was elevated by the 28-day treatment. However, the liver microsomal activities of the oxidation of the respective substrates of Cyp1a, Cyp2a, Cyp2b, Cyp2d, and Cyp2e1 remained unchanged. In the kidney, SJW increased the NFO, but not the WOH activity. The extended 28-day treatment did not alter mouse hepatic and renal UGT, GST, and NQO activities. These findings demonstrate that SJW stimulates hepatic and renal Cyp3a activity and hepatic Cyp2c activity and expression. The induction of hepatic Cyp2c requires repeated treatment for a period longer than the initial induction of Cyp3a. |
Databáze: | OpenAIRE |
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