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. Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone‐treated sheep. J. vet. Pharmacol. Therap. 35, 319–328. The effects of repeated ad...

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Published in:Journal of veterinary pharmacology and therapeutics 2012-08, Vol.35 (4), p.319-328
Main Authors: MATÉ, M. L, LIFSCHITZ, A, SALLOVITZ, J, BALLENT, M, MUSCHER, A. S, WILKENS, M. R, SCHRÖDER, B, LANUSSE, C, VIRKEL, G
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Blotting, Western
correlation
cytochrome P-450
Cytochrome P-450 CYP3A - genetics
Cytochrome P-450 CYP3A - metabolism
Dexamethasone - pharmacology
Electrophoresis, Polyacrylamide Gel - veterinary
erythromycin
gene expression
Gene Expression Regulation, Enzymologic - drug effects
genes
intestinal mucosa
Intestinal Mucosa - metabolism
isozymes
liver
Liver - enzymology
liver function
Male
messenger RNA
metabolism
polymerase chain reaction
Real-Time Polymerase Chain Reaction
RNA - genetics
RNA - metabolism
sheep
Sheep - metabolism
small intestine
transcription factors
Western blotting
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Summary:Maté, M. L., Lifschitz, A., Sallovitz, J., Ballent, M., Muscher, A. S., Wilkens, M. R., Schröder, B., Lanusse, C., Virkel, G. Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone‐treated sheep. J. vet. Pharmacol. Therap. 35, 319–328. 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, on 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. CYP 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 (RXRα) was 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 
ISSN:0140-7783
1365-2885
DOI:10.1111/j.1365-2885.2011.01334.x