Effects of illicit dexamethasone upon hepatic drug metabolizing enzymes and related transcription factors mRNAs and their potential use as biomarkers in cattle.
In cattle fattening, the illicit use of growth promoters (GPs) represents a major problem. The synthetic corticosteroid dexamethasone (DEX) is the GP mostly used, alone or in combination with other steroids or beta-agonists. Recently, GPs were shown to disrupt some cattle cytochromes P450 (CYPs) at the post-transcriptional level; therefore, the effects of two illicit protocols containing DEX (alone or together with 17beta-estradiol, 17betaE) upon main cattle liver drug metabolizing enzymes (DMEs) mRNAs and related transcription factors were investigated by quantitative real time RT-PCR. Eleven genes, out of the 18 considered, were significantly modulated by GPs. Corticosteroid-responsive genes did not respond univocally, whereas retinoic X receptor alpha (RXRalpha) and estrogen receptor alpha (ERalpha) were upregulated depending on the illicit protocol used. Nowadays, an increasing interest has been noticed toward the detection of biomarkers of response (BMRs) to be used in the screening of GPs misuse in cattle farming. In the present study, CYP2B6-like, CYP2E1, glutathione S-transferase A1- and sulfotransferase A1-like (GSTA1- and SULT1A1-like) mRNAs were significantly modulated regardless of the GP, the illicit protocol, and the animal breed, representing promising BMRs. The usefulness of these BMRs needs to be characterized more in depth.
Giantin
Mery
M
Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Università di Padova, I-35020 Agripolis Legnaro, Padova, Italy.
Lopparelli
Rosa M
RM
Zancanella
Vanessa
V
Martin
Pascal G
PG
Polizzi
Arnaud
A
Gallina
Guglielmo
G
Gottardo
Flaviana
F
Montesissa
Clara
C
Ravarotto
Licia
L
Pineau
Thierry
T
Dacasto
Mauro
M
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002417:Cattle / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015813:Substance Abuse Detection / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D015415:Biomarkers; D012333:RNA, Messenger; D014157:Transcription Factors; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase