Using 2-(2-Chlorophenyl)thiazolidine-4-carboxylic Acid as a Novel Biomarker for 2-Chlorobenzalmalononitrile Exposure.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Chemical Research in Toxicology Pub Date : 2024-10-21 Epub Date: 2024-10-05 DOI:10.1021/acs.chemrestox.4c00304
Guanrui Pan, Hei-Tak Tse, Ho-Wai Chan, Wan Chan
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引用次数: 0

Abstract

This study addressed the development of a novel biomarker for 2-chlorobenzalmalononitrile (CS) gas exposure. Using liquid chromatographic and mass spectrometric techniques, we found that CS underwent rapid hydrolysis into 2-chlorobenzaldehyde (2-CBA), a highly reactive intermediate that reacted swiftly with endogenous cysteine (Cys) and Cys residues in proteins, producing a stable 2-(2-chlorophenyl)thiazolidine-4-carboxylic acid adduct (ClPh-SPro) in high yield, which may be used as a CS exposure dosimeter. In particular, it was found that most CS was rapidly hydrolyzed under physiologically relevant conditions, with over 90% of CS being converted into 2-CBA in as short as 20 min. The resultant 2-CBA then reacted swiftly with Cys (k = 0.086 M-1 s-1), forming the stable thiazolidine-4-carboxylic acid adduct, which was detected both in the intracellular fluid and in the cell-isolated proteins of CS-exposed lung cells, as well as in purified human serum albumin. It is expected that the results of this study will facilitate exposure assessment for bystanders who may have been exposed to high levels of CS gas unwillingly.

将 2-(2-氯苯基)噻唑烷-4-羧酸用作暴露于 2-氯苯丙二腈的新型生物标记物
本研究旨在开发一种新型生物标记,用于检测 2-氯苯丙二腈(CS)气体暴露。利用液相色谱和质谱技术,我们发现 CS 会快速水解为 2-氯苯甲醛(2-CBA),这是一种高活性中间体,会迅速与蛋白质中的内源性半胱氨酸(Cys)和 Cys 残基发生反应,生成稳定的 2-(2-氯苯基)噻唑烷-4-羧酸加合物(ClPh-SPro),产量很高,可用作 CS 暴露剂量计。研究特别发现,在生理相关条件下,大部分 CS 会迅速水解,90% 以上的 CS 会在短短 20 分钟内转化为 2-CBA。随后,生成的 2-CBA 与 Cys 迅速发生反应(k = 0.086 M-1 s-1),形成稳定的噻唑烷-4-羧酸加合物,在细胞内液、暴露于 CS 的肺细胞的细胞分离蛋白以及纯化的人类血清白蛋白中都检测到了这种加合物。预计这项研究的结果将有助于对可能在不情愿的情况下暴露于高浓度 CS 气体的旁观者进行暴露评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
7.30%
发文量
215
审稿时长
3.5 months
期刊介绍: Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.
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