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首页> 外文期刊>Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research >Biological fate of styrene oxide adducts with globin: Elimination of cleavage products in the rat urine
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Biological fate of styrene oxide adducts with globin: Elimination of cleavage products in the rat urine

机译：珠脂蛋白加合物的生物命运：消除大鼠尿液中的切割产品

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The in vivo fate of globin adducts with styrene 7,8-oxide (SO), an electrophilic metabolic intermediate of styrene, was studied in male Wistar rats dosed intraperitoneally with racemic SO, 100 mg/kg b. w. Regioisomeric hydroxy(phenyl) ethyl (HPE) adducts at Cys, N-terminal Val, Lys and His in globin were determined and their elimination from blood was followed during 60 days, corresponding to life span of rat erythrocytes. In the rat urine, N alpha acetylated products of hydrolytic cleavage of the HPE adducts with Cys, Lys and His were determined. On the first day post-exposure, abundant N alpha-acetyl-HPE-Cys adducts (mercapturic acids) formed via direct conjugation of SO with hepatic glutathione were excreted rapidly, but then a much slower phase of elimination reflecting formation of Na-acetyl-HPE-Cys via cleavage of the adducted globin was observed. A two-phase elimination occurred also in urinary Na-acetyl-HPE adducts with His and Lys. While a decline by 75-85% during the first 7 days post-exposure most likely reflected elimination of adducted albumin, the subsequent slow decline until day 60 corresponded to elimination kinetics of the adducted globin. Thus, the study not only provided original data on the fate of SO-globin adducts but also allowed to reveal general toxicokinetics properties of the urinary cleavage products as a novel type of chemical exposure biomarkers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
机译：在腹膜内腹腔内用外消旋的大鼠研究珠曲蛋白的珠蛋白增合物的体内蛋白质加合物（SO），苯乙烯的亲电代谢中间体，用外消旋的大鼠，100mg / kg b。哇测定Cys，N-末端Val，Lys和他蛋白在Cys，N-末端Val，Lys和他叶片上的乙基（HPE）加合物，并在60天期间，对应于大鼠红细胞的寿命，从血液中取消。在大鼠尿液中，测定了HPE加合物的水解裂解的Nα乙酰化产物用Cys，Lys和他的水解裂解。在暴露后的第一天，通过直接缀合所以用肝谷胱甘肽形成的丰富的Nα-乙酰基-HPE-cys加合物（氟甲酸）迅速排出，然后在反射形成Na-乙酰基的形成较慢的消除阶段。观察到通过裂解加入珠蛋白的HPE-CYS。两相消除也发生在尿na-乙酰基-HPE与他和液体中加合物。虽然在暴露后的前7天内下降75-85％最有可能反映消除有机白蛋白，但随后的缓慢下降至第60天，相当于消除有机珠蛋白的动力学。因此，该研究不仅为上珠蛋白加合物的命运提供了原始数据，而且还允许揭示泌尿裂解产品的一般毒性学性质作为一种新型的化学曝光生物标志物。 （c）2016 Elsevier Ireland Ltd.保留所有权利。

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