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非法地塞米松对牛肝药物代谢酶及其相关转录因子 mRNA 的影响及其作为生物标志物的潜在用途。

Effects of illicit dexamethasone upon hepatic drug metabolizing enzymes and related transcription factors mRNAs and their potential use as biomarkers in cattle.

机构信息

Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Università di Padova, I-35020 Agripolis Legnaro, Padova, Italy.

出版信息

J Agric Food Chem. 2010 Jan 27;58(2):1342-9. doi: 10.1021/jf9033317.

DOI:10.1021/jf9033317
PMID:20041653
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.

摘要

在牛育肥过程中,非法使用生长促进剂(GPs)是一个主要问题。合成皮质甾醇地塞米松(DEX)是最常使用的 GP,单独使用或与其他类固醇或β-激动剂联合使用。最近,研究表明 GPs 会在转录后水平上破坏一些牛细胞色素 P450(CYPs);因此,通过定量实时 RT-PCR 研究了含有 DEX(单独或与 17β-雌二醇、17βE 一起)的两种非法方案对主要牛肝药物代谢酶(DMEs)mRNA 及其相关转录因子的影响。在考虑的 18 个基因中,有 11 个基因被 GPs 显著调节。皮质甾醇反应基因的反应并不一致,而视黄酸 X 受体α(RXRα)和雌激素受体α(ERα)则根据所使用的非法方案而上调。如今,人们对检测用于筛选牛养殖中 GP 滥用的反应生物标志物(BMRs)的兴趣日益增加。在本研究中,CYP2B6 样、CYP2E1、谷胱甘肽 S-转移酶 A1-和磺基转移酶 A1 样(GSTA1-和 SULT1A1-样)mRNA 无论 GP、非法方案和动物品种如何,均被显著调节,代表有前途的 BMRs。这些 BMRs 的有用性需要更深入地进行特征描述。

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