The toxic effects and fate of intravenously administered zearalenone in goats
The toxic effects and fate of intravenously administered zearalenone in goats
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DOI：
10.1016/j.toxicon.2009.10.004
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发表时间：
2010-02-01
期刊：
影响因子：
2.8
通讯作者：
Kumagai, S.
中科院分区：
文献类型：
--
作者：
Dong, M.;He, X. J.;Kumagai, S.
为了阐明玉米赤霉烯酮（ZEA）在反刍动物中的毒性作用和归宿，我们研究了山羊单次静脉注射2.4 mg/kg bw和1.2 mg/kg bw ZEA后的组织病理学变化和毒代动力学特征。还研究了组织中雌激素受体（ER）α和β的mRNA的表达。组织病理学研究表明，ZEA引起肝细胞肿胀以及肝脏、肾脏和子宫中的淋巴细胞浸润。ER α mRNA的表达增强与组织病理学改变相关，表明ER α可能参与了ZEA的毒性作用。对于毒代动力学特征，在静脉注射ZEA后连续采集血浆、尿液和粪便，并采用高效液相色谱法（HPLC）分析ZEA山羊及其代谢产物。用ZEA检测到α-玉米赤霉烯醇药理学（ZOL）和β-ZOL，但α-玉米赤霉醇（ZAL）、β-ZAL和玉米赤霉酮低于检测限。ZEA的分布半衰期（t（1/2 α））和消除半衰期（t（1/2 β））分别为3.15和28.58 h。ZEA、α-ZOL和β-ZOL经尿液和粪便排泄。其中β-ZOL是主要代谢物。尿液中的ZEA和ZOL主要以葡糖苷酸和/或硫酸盐结合形式存在，而粪便中的ZEA和ZOL主要以游离形式存在。本研究揭示了玉米赤霉烯酮及其代谢产物在山羊体内的毒性作用及其药代动力学特征。(C)2009爱思唯尔有限公司保留所有权利。
To clarify the toxic effects and fate of zearalenone (ZEA) in ruminants, we studied histopathological changes and toxicokinetic profiles in goats administered with a single intravenous (iv) injection of ZEA at doses of 2.4 mg/kg bw and 1.2 mg/kg bw, respectively. The expression of the mRNA of estrogen receptor (ER) alpha and beta in tissues was also investigated. The histopathological study revealed that ZEA caused hepatocellular swelling and lymphocytic infiltration in the liver, kidney, and uterus. The expression of ER alpha mRNA was enhanced by ZEA in association with the histopathological changes, indicating the possible involvement of ER alpha in the toxic effects of ZEA. For toxicokinetic profiles, blood plasma, urine, and feces were collected consecutively after iv injection of ZEA and analyzed for ZEA Goat and its metabolites with high performance liquid chromatography (HPLC). alpha-Zearalenol Histopathology (ZOL) and beta-ZOL were detected with ZEA, but alpha-zearalanol (ZAL), beta-ZAL, and zearalanone were below the detection limits. The distribution half-life (t(1/2 alpha)) and elimination half-life (t(1/2 beta)) of ZEA were 3.15 and 28.58 h, respectively. ZEA, alpha-ZOL, and beta-ZOL were excreted in urine and feces. with beta-ZOL being the predominant metabolite. The ZEA and ZOL in urine were largely in their glucuronide and/or sulphate conjugated forms, while those in feces were largely in their free forms. This study showed the toxic effect of zearalenone and its metabolites, and their pharmacokinetic characteristics in goats. (C) 2009 Elsevier Ltd. All rights reserved.