Cytochrome P450 inhibition profile in liver of veal calves administered a combination of 17beta-estradiol, clenbuterol, and dexamethasone for growth-promoting purposes.
The effects of the administration of a combination of 17beta-estradiol (10mg i.m. for three times at 17 days intervals), dexamethasone (4 mg/day for 6 days and 5mg/day for further 6 days, dissolved in milk), and clenbuterol (20 microg/kg b.w./day, dissolved in milk, for the last 40 days before slaughtering) for growth-promoting (GP) purposes on liver drug metabolising capacity were studied in crossbred Friesian male calves. Compared to controls, liver preparations from GP-treated calves showed an overall reduction in the extent of the in vitro ability to metabolize testosterone and a number of substrates, most notably those associated with CYP 2C or CYP 3A, which also displayed a reduced expression on western blotting. By contrast, the tested hydrolytic and conjugative pathways were not significantly affected. As measured by northern blot, the lack of significant differences in CYP mRNA abundance point to a post-transcriptional effect of the GP combination. The remarkable involvement of the affected hepatic CYPs in the biotransformation of both steroid hormones and a large array of commonly used drugs may result in the further accumulation of undesirable residues in meat and offals of illegally treated calves.
Cantiello
Michela
M
Dipartimento di Patologia Animale, Sezione di Farmacologia e Tossicologia, Università di Torino, Via Leonardo da Vinci 44, 10095 Grugliasco (TO), Italy.
Carletti
Monica
M
Dacasto
Mauro
M
Martin
Pascal G P
PG
Pineau
Thierry
T
Capolongo
Francesca
F
Gardini
Giulia
G
Nebbia
Carlo
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002417:Cattle; D002976:Clenbuterol / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D004958:Estradiol / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006128:Growth / Q000187:drug effects*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D013268:Stimulation, Chemical; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D065607:Cytochrome P-450 Enzyme Inhibitors; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D004958:Estradiol; D012313:RNA; D003907:Dexamethasone; D009251:NADPH-Ferrihemoprotein Reductase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D002265:Carboxylic Ester Hydrolases; D002976:Clenbuterol