Effects of Illicit Dexamethasone upon Hepatic Drug Metabolizing Enzymes and Related Transcription Factors mRNAs and Their Potential Use As Biomarkers in Cattle

Abstract

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.

Absolute quantification and modulation of cytochrome P450 3A isoforms in cattle liver

“…In cattle, the order of magnitude of PB induction was two-to four-times the control value and comparable to the more general CYP3A pattern of up-regulation (Zancanella et al, 2012). Present and previously published data (Greger et al, 2006;Cantiello et al, 2009;Giantin et al, 2010;Zancanella et al, 2012) suggest that differences in CYP3A regulation, expression and function may perhaps exist between cattle and humans. Such a hypothesis is fascinating and worthy of further molecular studies.…”

Transcriptomic markers meet the real world: finding diagnostic signatures of corticosteroid treatment in commercial beef samples

“…Initially, quantitative real-time PCR was used to analyze the expression of candidate diagnostic genes. This approach has already been successfully applied in several studies on experimentally treated animals [7-12]. However, good candidate genes are often difficult to identify and the use of single or few gene markers provides a limited and biased view of the biological response to xenobiotics.…”

Progesterone receptor up-regulation: a diagnostic tool for the illicit use of oestrogens in adult beef cattle

“…A number of novel gene expression profiles have been examined in different bovine tissues, and some of these findings could be applicable in the field as routine screening methods (Toffolatti et al 2006;Reiter et al 2007;Carraro et al 2009;Giantin et al 2010;Lopparelli et al 2010). Recently, De Maria et al (2010 investigated PR mRNA expression in bulbourethral glands as a potential biomarker of illicit 17-oestradiol administration in veal calves and found that it may be a promising new approach to improve the current residue control programmes.…”