In the European Community, the use of growth promoters (GPs) to increase animai performances in cattle is forbidden (Dir. CEE 96/22 and 96/23); nonetheless, the illicit use of GPs, like anabolic steroids, B-agonists or corticosteroids like dexamethasone (DX), still represents a major concem in this food-producing species (4). Nowadays, increasing importance is attributed to "ornie" methodologies useful to define biomarkers (BMs); in this respect, an increasing interest toward the setting-up of BMs to assist official analytical methods in illieit GPs screening was recently signalled in cattle (2-3). micit GPs may affect drug metabolizing enzymes (DMEs) post-transcriptionally (1); therefore, the pretranscriptional effects of two illicit protocols containing DX, upon relevant DMEs genes and transcription factors, were investigated. Small aliquots of liver tissue were obtained from male beef cattle, untreated or administered either with DX (given im or per os) or a cocktail consisting of DX (per os) and 17~-oestradiol (E2, im). Routes of administration and dosage regimens were similarto those iIlegally used in the field. Seventeen candidate genes were selected according to their relevance in drug metabolism, including both phase I and II DMEs (cytochrome P450s and glutathione- or glucuronyl-transferases, respectively) as well as transcription factors. For each gene, the corresponding bovine sequence was obtained and a genespecific quantitative real-time PCR assay was optimised and validated. As a whole, in the liver of treated cattle the expression of 8 target genes, out of the 17 tested, were significantly influenced by GPs: six when DX was administered alone and 7 in the case of DX plus E2. Moreover, an overall and significant down-regulation of CYP2B6 and CYP2El gene expression profile was recorded, independently from the GP, the route of administration and the dosage regimen adopted. Present results indicate that some GPs (DX, E2) are likely to modulate liver DMEs at the pre-transcriptionallevel in cattle; besides, the gene expression profiling might represents a feasible approach for the screening of GPs used iIlicitly. This study represents a preliminary work for the development of a set of hepatic biomarkers to be used in the field monitoring, that should be improved increasing the number of candidates and validating them on a greater amounts of controls. ACKNOWLEDGMENT Supported by grants from Ministero della Salute (IZS.VE.009/03RC),Università degli Studi di Padova (CPDA054599) and Università ltalo-Francese (Programma Galileo 2006).

Effects of dexamethasone illicit treatments upon cattle liver drug metabolizing enzymes gene expression and regulation

GIANTIN, MERY;LOPPARELLI, ROSA MARIA;MONTESISSA, CLARA;DACASTO, MAURO
2008

Abstract

In the European Community, the use of growth promoters (GPs) to increase animai performances in cattle is forbidden (Dir. CEE 96/22 and 96/23); nonetheless, the illicit use of GPs, like anabolic steroids, B-agonists or corticosteroids like dexamethasone (DX), still represents a major concem in this food-producing species (4). Nowadays, increasing importance is attributed to "ornie" methodologies useful to define biomarkers (BMs); in this respect, an increasing interest toward the setting-up of BMs to assist official analytical methods in illieit GPs screening was recently signalled in cattle (2-3). micit GPs may affect drug metabolizing enzymes (DMEs) post-transcriptionally (1); therefore, the pretranscriptional effects of two illicit protocols containing DX, upon relevant DMEs genes and transcription factors, were investigated. Small aliquots of liver tissue were obtained from male beef cattle, untreated or administered either with DX (given im or per os) or a cocktail consisting of DX (per os) and 17~-oestradiol (E2, im). Routes of administration and dosage regimens were similarto those iIlegally used in the field. Seventeen candidate genes were selected according to their relevance in drug metabolism, including both phase I and II DMEs (cytochrome P450s and glutathione- or glucuronyl-transferases, respectively) as well as transcription factors. For each gene, the corresponding bovine sequence was obtained and a genespecific quantitative real-time PCR assay was optimised and validated. As a whole, in the liver of treated cattle the expression of 8 target genes, out of the 17 tested, were significantly influenced by GPs: six when DX was administered alone and 7 in the case of DX plus E2. Moreover, an overall and significant down-regulation of CYP2B6 and CYP2El gene expression profile was recorded, independently from the GP, the route of administration and the dosage regimen adopted. Present results indicate that some GPs (DX, E2) are likely to modulate liver DMEs at the pre-transcriptionallevel in cattle; besides, the gene expression profiling might represents a feasible approach for the screening of GPs used iIlicitly. This study represents a preliminary work for the development of a set of hepatic biomarkers to be used in the field monitoring, that should be improved increasing the number of candidates and validating them on a greater amounts of controls. ACKNOWLEDGMENT Supported by grants from Ministero della Salute (IZS.VE.009/03RC),Università degli Studi di Padova (CPDA054599) and Università ltalo-Francese (Programma Galileo 2006).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2436439
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