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乙苯代谢中的谷胱甘肽途径:大鼠暴露的新型生物标志物。

Glutathione pathway in ethylbenzene metabolism: novel biomarkers of exposure in the rat.

机构信息

Institut National de Recherche et de Sécurité (INRS), Rue du Morvan CS 60027, Vandoeuvre, 54519 Cedex, France.

出版信息

Chemosphere. 2010 Nov;81(10):1334-41. doi: 10.1016/j.chemosphere.2010.08.025. Epub 2010 Sep 9.

DOI:10.1016/j.chemosphere.2010.08.025
PMID:20825968
Abstract

Glutathione pathway was specifically studied in rats exposed by inhalation to a range of ethylbenzene vapours (5-2000 ppm). Urines were collected during exposure (6h) and over the 18 h following the exposure. The potential metabolites coming from either side-chain or ring oxidation were synthesized: 1-, 2-phenylethylmercapturic acids (1-, and 2-PEMA) and 2-, 3- and 4-ethylphenylmercapturic acids (2-, 3-, and 4-EPMA). Their synthesis was fully described and the molecules characterized. Urine samples were analysed using a selective HPLC-fluorescence method. Among the five metabolites, 2-PEMA was never observed in any urine sample. By contrast, 1-PEMA was discovered in its two diastereomeric forms, and it was shown that one of them was mainly present. 2-EPMA, 3-EPMA and 4-EPMA (in the ratio 1:2:6) were also found, and their combined excretion levels were similar to that of 1-PEMA. The atmospheric concentrations and urinary excretions yielded very close correlations which allow us to consider these mercapturic acids as novel ethylbenzene exposure biomarkers.

摘要

谷胱甘肽途径在吸入范围内的乙基苯蒸气(5-2000 ppm)暴露的大鼠中进行了专门研究。在暴露期间(6 小时)和暴露后 18 小时内收集尿液。从侧链或环氧化合成了潜在的代谢产物:1-、2-苯乙基硫代尿酸(1-和 2-PEMA)和 2-、3-和 4-乙基苯硫代尿酸(2-、3-和 4-EPMA)。它们的合成得到了充分的描述,并对分子进行了表征。使用选择性 HPLC-荧光法分析尿液样品。在这五种代谢物中,2-PEMA 从未在任何尿液样本中观察到。相比之下,1-PEMA 以两种非对映异构体的形式被发现,并且表明其中一种主要存在。还发现了 2-EPMA、3-EPMA 和 4-EPMA(比例为 1:2:6),它们的联合排泄水平与 1-PEMA 相似。大气浓度和尿液排泄之间存在非常密切的相关性,这使我们能够将这些硫代尿酸视为新型的乙基苯暴露生物标志物。

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