Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone-treated sheep

MATÉ, M.L.; LIFSCHITZ, A.; SALLOVITZ, J.; BALLENT, M.; MUSCHER, A.S.; WILKENS, M.R.; SCHRÖDER, B.; LANUSSE, C.; VIRKEL, G.

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 vol. 35 p. 319 - 328

0140-7783

The effects of repeated administrations of dexamethasone (DEX) (3 mg/kg/day by IM route for 7 days) on the gene expression profile of a cytochrome P450 (CYP) 3A28-like isoenzyme, the expression of a CYP3A immunoreactive protein, and on CYP3A-dependent metabolic activities in sheep liver and small intestinal mucosa were evaluated in the current work. Cytochrome P450 3A-dependent metabolic activities (erythromycin and triacetyl-oleandomycin N-demethylations) were assessed in microsomal fractions. The mRNA expression of CYP3A28-like, glucocorticoid receptor, constitutive androstane receptor, pregnane X receptor and retinoic X receptor alpha were determined by quantitative Real-Time PCR. The expression of a CYP3A immunoreactive protein was measured by Western blot analyses. In the liver, DEX treatment increased CYP3A28-like mRNA levels (2.67-fold, p