title: Clofibric acid induces hepatic CYP 2B1/2 via constitutive androstane receptor not via peroxisome proliferator activated receptor alpha in rat.
abstract: Peroxisome proliferator activated receptor α (PPARα) ligands, fibrates used to control hyperlipidemia. We demonstrated CYP2B induction by clofibric acid (CFA) however, the mechanism was not clear. In this study, HepG2 cells transfected with expression plasmid of mouse constitutive androstane receptor (CAR) or PPARα were treated with CFA, phenobarbital (PB) or TCPOBOP. Luciferase assays showed that CFA increased CYP2B1 transcription to the same level as PB, or TCPOBOP in HepG2 transfected with mouse CAR But failed to induce it in PPARα transfected cells. CYP2B expressions were increased with PB or CFA in Wistar female rats (having normal levels of CAR) but not in Wistar Kyoto female rats (having low levels of CAR). The induction of CYP2B by PB or CFA was comparable to nuclear CAR levels. CAR nuclear translocation was induced by CFA in both rat strains. This indicates that fibrates can activate CAR and that fibrates-insulin sensitization effect may occur through CAR, while hypolipidemic effect may operate through PPARα.
authors: a Faculty of Veterinary Medicine, Department of Physiology , Kafrelsheikh University , Kafrelsheikh , Egypt.
authors: Zein Shaban
authors: ZS
authors: Ibrahim
authors: Mohamed Mohamed
authors: MM
authors: Ahmed
authors: Samir Ahmed
authors: SA
authors: El-Shazly
authors: Mayumi
authors: M
authors: Ishizuka
authors: Shoichi
authors: S
authors: Fujita
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D002995:Clofibric Acid / Q000008:administration & dosage*; D000090702:Constitutive Androstane Receptor; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics; D010634:Phenobarbital / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
chemical_list: D000090702:Constitutive Androstane Receptor; D007328:Insulin; D047493:PPAR alpha; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; D002995:Clofibric Acid; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1; C025619:steroid 16-beta-hydroxylase; D010634:Phenobarbital
keywords: CYP2B, constitutive androstane receptor (CAR); clofibric acid (CFA); peroxisome proliferator receptor α (PPARα), rats