PMID- 35255248 OWN - NLM STAT- Publisher LR - 20231013 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 234 DP - 2022 Apr 1 TI - A high-throughput assay for screening the abilities of per- and polyfluoroalkyl substances in inducing plasma kallikrein-like activity. PG - 113381 LID - S0147-6513(22)00221-4 [pii] LID - 10.1016/j.ecoenv.2022.113381 [doi] AB - The plasma consists of multiple functional serine zymogens, such as plasma kallikrein-kinin system (KKS), which are vulnerable to exogenous chemical exposure, and may closely relate to the deleterious effects. Testing whether the anthropogenic chemicals could increase the kallikrein-like activity in plasma or not would be of great help to understand their potentials in triggering the cascade activation of the plasma zymogens and explain the corresponding hematotoxicity. In this study, a novel high-throughput ex vivo assay was established to screen the abilities of emerging chemicals like per- and polyfluoroalkyl substances (PFASs) in inducing kallikrein-like activities on basis of using rat plasma as the protease zymogen source. Upon the optimization of the conditions in the test system, the assay gave sensitive fluorescent response to the stimulation of the positive control, dextran sulfate, and the dose-response showed a typical S-shaped curve with EC(50) of 0.24 mg/L. The intra-plate and inter-plate relative standard deviations (RSDs) were less than 10% in the quantitative range of dextran sulfate, indicating a good reliability and repeatability of this newly-established assay. Using this method, several alternatives or congeners of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), including 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA), Ag-PFOA, K-PFOA, Na-PFOA and ammonium pentadecafluorooctanoate (APFO), were further screened, and their capabilities in inducing kallikrein-like activities were identified. The ex vivo assay newly-developed in the present study would be promising in high-throughput screening of the hematological effects of emerging chemicals of concern. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Liu, Qian S AU - Liu QS AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. FAU - Zhang, Yuzhu AU - Zhang Y AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Sun, Zhendong AU - Sun Z AD - School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310000, China. FAU - Gao, Yurou AU - Gao Y AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Zhou, Qunfang AU - Zhou Q AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Environment and Health, Jianghan University, Wuhan 430056, China. Electronic address: zhouqf@rcees.ac.cn. FAU - Jiang, Guibin AU - Jiang G AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China. LA - eng PT - Journal Article DEP - 20220304 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 SB - IM OTO - NOTNLM OT - Ex-vivo assay OT - Hematological effects OT - High-throughput screening OT - Kallikrein-like activity OT - Per- and polyfluoroalkyl substances EDAT- 2022/03/08 06:00 MHDA- 2022/03/08 06:00 CRDT- 2022/03/07 20:08 PHST- 2021/10/24 00:00 [received] PHST- 2022/02/23 00:00 [revised] PHST- 2022/03/01 00:00 [accepted] PHST- 2022/03/08 06:00 [pubmed] PHST- 2022/03/08 06:00 [medline] PHST- 2022/03/07 20:08 [entrez] AID - S0147-6513(22)00221-4 [pii] AID - 10.1016/j.ecoenv.2022.113381 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2022 Apr 1;234:113381. doi: 10.1016/j.ecoenv.2022.113381. Epub 2022 Mar 4.