Wang Qiao, Chen Xinyu, Ren Yiping, Chen Qing, Meng Zhen, Cheng Jun, Zheng Yunyan, Zeng Weijiang, Zhao Qingning, Zhang Yu
Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Yangtze Delta Region Institute of Tsinghua University, Jiaxing, 314006, Zhejiang, China.
Arch Toxicol. 2017 May;91(5):2107-2118. doi: 10.1007/s00204-016-1869-6. Epub 2016 Oct 13.
Acrylamide is classified as a probable carcinogen to humans and generated from Maillard reaction. Currently, the short-term exposure to acrylamide was evaluated via external diet sources in vitro or two main mercapturic acid metabolites: N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) in vivo. In the present work, we comprehensively profiled four mercapturic acid metabolites and evaluated their internal exposure in rats and Chinese adolescents. The cumulative excretion of mercapturic acid metabolites contributes 38.4-73.0 and 43.8-63.6 % of total in vivo metabolites of acrylamide in male and female rats, respectively, when 1, 10, and 50 mg/kg bw of acrylamide were orally administered. Toxicokinetic study revealed that the conversion of acrylamide into glycidamide and glutathione coupling process is highly related to the gender and oral gavage dose via evaluating kinetic parameters, accumulative excretion percentages, and molar ratios of oxidative to reductive metabolism. In human study, a total of 101 Chinese adolescents (41 men and 60 women) were enrolled and served with a meal of potato chips, corresponding to a single-dose (12.6 μg/kg bw) exposure to acrylamide. Toxicokinetic work showed that AAMA is an early and predominant metabolite appearing as a biomarker in urine. N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), an oxidative product from AAMA, exhibits a higher peak concentration than GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA) during the whole 48-h toxicokinetic period. The internal exposure via four mercapturic acid metabolites is associated with the gender and body mass index characteristics. Thus, current study aims at mercapturic acid metabolites as urinary biomarkers and provides comprehensive insights into the short-term internal exposure to acrylamide.
丙烯酰胺被归类为对人类可能的致癌物，由美拉德反应产生。目前，通过体外饮食来源或体内两种主要的硫醚氨酸代谢物：N-乙酰-S-(2-氨甲酰基乙基)-L-半胱氨酸（AAMA）和N-乙酰-S-(2-氨甲酰基-2-羟乙基)-L-半胱氨酸（GAMA）来评估丙烯酰胺的短期暴露。在本研究中，我们全面分析了四种硫醚氨酸代谢物，并评估了它们在大鼠和中国青少年体内的内暴露情况。当分别以1、10和50mg/kg体重的剂量口服丙烯酰胺时，硫醚氨酸代谢物的累积排泄量分别占雄性和雌性大鼠体内丙烯酰胺总代谢物的38.4-73.0%和43.8-63.6%。毒代动力学研究表明，通过评估动力学参数、累积排泄百分比以及氧化代谢与还原代谢的摩尔比，丙烯酰胺向环氧丙酰胺的转化和谷胱甘肽偶联过程与性别和灌胃剂量高度相关。在人体研究中，共招募了101名中国青少年（41名男性和60名女性），并让他们食用了一份薯片，相当于单次剂量（12.6μg/kg体重）暴露于丙烯酰胺。毒代动力学研究表明，AAMA是尿液中出现的一种早期且主要的代谢物生物标志物。AAMA的氧化产物N-乙酰-S-(2-氨甲酰基乙基)-L-半胱氨酸亚砜（AAMA-sul）在整个48小时的毒代动力学期间，其峰值浓度高于GAMA和N-乙酰-S-(1-氨甲酰基-2-羟乙基)-L-半胱氨酸（异-GAMA）。通过四种硫醚氨酸代谢物的内暴露与性别和体重指数特征相关。因此，本研究旨在将硫醚氨酸代谢物作为尿液生物标志物，并为丙烯酰胺的短期体内暴露提供全面的见解。
