Quantitative urinalysis of the mercapturic acid conjugates of allyl formate using high-resolution NMR spectroscopy

Quantitative urinalysis of the mercapturic acid conjugates of allyl formate using high-resolution NMR spectroscopy
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DOI:
10.1016/j.jpba.2005.06.039
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发表时间:
2006-02-13
影响因子:
3.4
通讯作者:
Nicholson, JK
Nicholson, JK
中科院分区:
医学3区
文献类型:
--
作者:
Athersuch, TJ;Keun, H;Nicholson, JK

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巯基尿酸(MCAs)是谷胱甘肽结合异生素代谢的终产物,可作为指示烯丙基化合物暴露及其排泄速率和效率的标志物。此外,某些MCAs的形成表明通过已知的毒素丙烯醛(一种强亲电试剂)进行代谢。采用高分辨率H-1 NMR光谱定量测定Sprague-Dawley大鼠腹腔注射25和50 mg/kg(-1)甲酸烯丙酯(AF)(一种模型毒素)后8小时内尿液中MCA的存在。3-发现羟丙基巯基尿酸(HPMA)是尿液中排泄的唯一H-1 NMR可观察到的MCA,在25 mg kg(-1)剂量水平下的回收率接近20%,在50 mg kg(-1)剂量水平下为-30%。(c)2005 Elsevier B. V.保留所有权利。
As end products of xenobiotic metabolism via glutathione conjugation, mercapturic acids (MCAs) can be used as markers to indicate exposure to allylic compounds as well as the rate and efficiency of their excretion. In addition, the formation of certain MCAs indicates metabolism via the known toxin acrolein, a strong electrophile. High-resolution H-1 NMR spectroscopy has been employed to quantitatively measure the presence of MCAs in the urine of Sprague-Dawley rats, collected in the 8h following 25 and 50 mg kg(-1) i.p. doses of allyl formate (AF), a model toxin. 3-Hydroxypropylmercapturic acid (HPMA) was found to be the only H-1 NMR-observable MCA excreted in the urine, exhibiting a percentage recovery of similar to 20% at the 25 mg kg(-1) dose level, and -30% at the 50 mg kg(-1) dose level. (c) 2005 Elsevier B.V. All rights reserved.