Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine; Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Laboratory of Chemistry and Physics, Hangzhou Center for Disease Control and Prevention, Hangzhou 310021, Zhejiang, China.
Sci Total Environ. 2024 Apr 10;920:170946. doi: 10.1016/j.scitotenv.2024.170946. Epub 2024 Feb 14.
Furan represents one of the dietary-sourced persistent organic pollutants and thermal processing contaminants. Given its widespread occurrence in food and various toxicological effects, accurately assessing furan exposure is essential for informing public health risks. Furan is metabolized to a reactive primary product, cis-2-butene-1,4-dial (BDA) upon absorption. Some of the resulting BDA-derived metabolites have been proposed as potential exposure biomarkers of furan. However, the lack of quantification for recognized and feasible furan biomarkers has hampered the development of internal exposure risk assessment of furan. In this study, we employed reliable non-targeted metabolomics techniques to uncover urinary furan metabolites and elucidate their chemical structures. We characterized 8 reported and 11 new furan metabolites derived from the binding of BDA with glutathione (GSH), biogenic amines, and/or amino acids in the urine of male rats subjected to varying doses of furan. Notably, a mono-GSH-BDA adduct named cyclic GSH-BDA emerged as a highly prospective specific biomarker of furan exposure, as determined by an ultrahigh-performance liquid chromatography-tandem mass spectrometry method. Cyclic GSH-BDA demonstrated a robust mass spectrometry ion response intensity and exhibited evident time- and dose response. Additionally, we conducted a comprehensive profiling of the kinetics of potential furan biomarkers over time to capture the metabolic dynamics of furan in vivo. Most urinary furan metabolites reached peak concentrations at either the first (3 h) or second (6 h) sampling time point and were largely eliminated within 36 h following furan treatment. The present study provides novel insights into furan metabolism and sheds light on the biomonitoring of furan exposure.
呋喃是饮食来源的持久性有机污染物和热加工污染物之一。鉴于其在食品中的广泛存在和各种毒理学效应，准确评估呋喃暴露对于告知公众健康风险至关重要。呋喃在吸收后被代谢为活性的初级产物顺式-2-丁烯-1,4-二醛（BDA）。一些由此产生的 BDA 衍生代谢物已被提议作为呋喃暴露的潜在生物标志物。然而，由于缺乏对公认和可行的呋喃生物标志物的定量分析，阻碍了呋喃内暴露风险评估的发展。在这项研究中，我们采用可靠的非靶向代谢组学技术来揭示尿液中的呋喃代谢物并阐明其化学结构。我们对暴露于不同剂量呋喃的雄性大鼠尿液中 BDA 与谷胱甘肽（GSH）、生物胺和/或氨基酸结合产生的 8 种报告的和 11 种新的呋喃代谢物进行了表征。值得注意的是，一种名为环状 GSH-BDA 的单-GSH-BDA 加合物被确定为呋喃暴露的高度有前景的特异性生物标志物，这是通过超高效液相色谱-串联质谱法确定的。环状 GSH-BDA 表现出强大的质谱离子响应强度，并表现出明显的时间和剂量反应。此外，我们对潜在呋喃生物标志物的动力学进行了全面分析，以捕捉呋喃在体内的代谢动态。大多数尿液中的呋喃代谢物在第一次（3 小时）或第二次（6 小时）采样时间点达到峰值浓度，并在呋喃处理后 36 小时内基本消除。本研究为呋喃代谢提供了新的见解，并为呋喃暴露的生物监测提供了依据。
