Induction of CYP3As in HepG2 Cells by Several Drugs. : Association between Induction of CYP3A4 and Expression of Glucocorticoid Receptor
スポンサーリンク
概要
- 論文の詳細を見る
The cytochrome P-450 3A (CYP3A) enzyme family is responsible for most of the drug metabolism in the human liver. In this study, we demonstrated the inductive effects of phenobarbital, rifampicin, carbamazcpine, phenytoin, prednisolone, ciclosporin and clotrimazole on CYP3A4, CYP3A5 and CYP3A7 mRNA expression, and established the relationship between the expression of human glucocorticoid receptor a (hGR) mRNA and the induction of CYP3A4 mRNA in cultured HepG2 cells by reverse transcription polymerase chain reaction (RT-PCR). Treatment with prednisolone, rifampicin and carbamazepine rapidly induced the level of CYP3A4 mRNA expression by 3- to 6-fold. However, phenytoin and phenobarbital gradually induced CYP3A4 mRNA level by 3 to 4-fold. The induction of CYP3A4 mRNA expression by clotrimazole and ciclosporin was negligible. Treatment with phenytoin, rifampicin, carbamazepine and ciclosporin induced approximately 2-fold increases in the expression of CYP3A5 mRNA, although prednisolone, phenytoin and clotrimazole had no effect. Treatment with rifampicin, phenytoin, clotrimazole and ciclosporin resulted in approximately a 2-fold induction of the CYP3A7 mRNA level. Treatment with rifampicin and ciclosporin induced the expression of hGRα mRNA significantly in comparison with controls, although the induction of hGRα mRNA following treatment with other drugs was negligible. In cluster analysis, the induced level of CYP3A4, CYP3A5, CYP3A7 and hGRα mRNA by these drugs could be classified into four major clusters. This suggested that each cluster might be associated with different mechanism(s) of induction by these drugs. Furthermore, we studied the associations between the expression of hGRα mRNA and the induced level of CYP3A4 mRNA by prednisolone and ciclosporin. Treatment with both prednisolone and ciclosporin showed synergistic effects on induction of CYP3A4 mRNA and, following treatment with both drugs, the expression level of CYP3A4 mRNA was 2-fold greater compared with prednisolone alone after the fifth day. Positive correlations were observed between the levels of hGRα mRNA expression and those of CYP3A4 mRNA. This observation shows that the regulation of CYP3A4 gene expression was hGRα-dependent and that ciclosporin may function as a regulator of expression via hGRα.
- 公益社団法人日本薬学会の論文
- 2003-04-01
著者
-
KOMADA Fusao
Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Josai University
-
SAITOH Yukiya
Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Josai University
-
Komada Fusao
Japan And Department Of Drug Informatics Faculty Of Pharmaceutical Sciences Jyosai University
-
Komada Fusao
Department Of Pharmacy Kyoto University Hospital Faculty Of Medicine Kyoto University
-
Usui Takashi
Drug Metabolism Laboratories Drug Development Division Yamanouchi Pharmaceutical Co. Ltd.
-
Komada F
Department Of Pharmacy Kobe University School Of Medicine
-
Saitoh Yukiya
Japan And Department Of Drug Informatics Faculty Of Pharmaceutical Sciences Jyosai University
-
Usui T
Drug Metabolism Research Laboratories Astellas Pharma Inc.
-
USUI Tatsuhiro
Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Josai University
関連論文
- Intradermal Concentration of Hydroquinone after Application of Hydroquinone Ointments Is Higher than Its Cytotoxic Concentration(Biopharmacy)
- SYNTHESIS AND BIOLOGICAL ACTIVITY OF THE NOVEL SULFATED AND PHOSPHORYLATED BIVALENT β-D-GALACTOPYRANOSIDES CONTAINING FATTY-ALKYL RESIDUES
- Comparative Study of Superoxide Dismutase in Normal and Hereditary Cataract (UPL) Rats
- Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)
- Interaction of Docetaxel ("Taxotere") with Human P-Glycoprotein
- Cellular Pharmacokinetic Aspects of Reversal Effect of Itraconazole on P-Glycoprotein-Mediated Resistance of Anticancer Drugs
- Inhibitory Effects of a Cyclosporin Derivative, SDZ PSC 833, on Transport of Doxorubicin and Vinblastine via Human P-Glycoprotein
- FATE OF PORCINE AND HUMAN INSULIN AT THE SUBCUTANEOUS INJECTION SITE. II. IN VITRO DEGRADATION OF INSULINS IN THE SUBCUTANEOUS TISSUE OF THE RAT
- FATE OF PORCINE AND HUMAN INSULIN AT THE SUBCUTANEOUS INJECTION SITE. I. DEGRADATION AND ABSORPTION OF INSULINS IN THE RAT
- FATE OF PORCINE AND HUMAN INSULIN IN SUBCUTANEOUSLY ADMINISTERED SITE
- N-Acetyltransferase2 Genotype Correlated with Isoniazid Acetylation in Japanese Tuberculous Patients
- Effects of Secretable SOD Delivered by Genetically Modified Cells on Xanthine/Xanthine Oxidase and Paraquat-Induced Cytotoxicity in Vitro
- Effects of Cu, Zn-Superoxide Dismutase Delivered by Genetically Modified Skin Fibroblasts on Cold-Induced Skin Edema in Rats
- Protective Effect of Transfection with Secretable Superoxide Dismutase (SOD) (a Signal Sequence-SOD Fusion Protein Coding cDNA) Expression Vector on Superoxide Anion-Induced Cytotoxicity in Vitro)
- Effect of Transfection with a Superoxide Dismutase Expression Plasmid on Xanthine/Xanthine Oxidase-Induced Cytotoxicity in Cultured Rat Lung Cells
- Pharmaceutical Studies for Gene Therapy : Expression of Human Cu, Zn-Superoxide Dismutase Gene Transfected by Lipofection in Rat Skin Fibroblasts
- Effect of Clarithromycin on the Bioavailability of Cyclosporin in Rats
- Effect of Transfection with Superoxide Dismutase Expression Plasmid on Superoxide Anion Induced Cytotoxicity in Cultured Rat Lung Cells
- Improvement in Wound Healing by Epidermal Growth Factor (EGF) Ointment. II. Effect of Protease Inhibitor, Nafamostat, on Stabilization and Efficacy of EGF in Burn
- Effects of Various Storage Conditions and Alterations of Antioxidant Contents on Chromatic Aberration of Hydroquinone Ointment(Biopharmacy)
- N-Acetyltransferase 2 Genotype-Related Sulfapyridine Acetylation and Its Adverse Events
- Sufficient effect of 1-week omeprazole and amoxicillin dual treatment for Helicobacter pylori eradication in cytochrome P450 2C19 poor metabolizers
- Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer(Biopharmacy)
- Pharmaceutical and Clinical Assessment of Hydroquinone Ointment Prepared by Extemporaneous Nonsterile Compounding
- Pharmacokinetic and Pharmacodynamic Analysis of the Antihypercalcemic Effect of Incadronate Disodium in Rats
- Generation of Superoxide Anions during the Reaction of Guanidino Compounds with Mehylglyoxal
- The Novel Anticancer Drug KRN5500 Interacts with, but is Hardly Transported by, Human P-Glycoprotein
- The Generation of Lucigenin Chemiluminescence from the Reaction of Guanidino Compounds with Phenylglyoxal under Alkaline Conditions and Its Application
- Electrophysiological Studies on the Evaluation of Absorption Enhancers in Caco-2 Cells Using a Microelectrode Technique
- Assessment of Chimeric Mice with Humanized Liver as a Tool for Predicting Circulating Human Metabolites
- Effect of Mixing Method on the Mixing Degree during the Preparation of Triturations
- Induction of CYP3As in HepG2 Cells by Several Drugs. : Association between Induction of CYP3A4 and Expression of Glucocorticoid Receptor
- Identification of Enzymes Responsible for the N-Oxidation of Darexaban Glucuronide, the Pharmacologically Active Metabolite of Darexaban, and the Glucuronidation of Darexaban N-Oxides in Human Liver Microsomes