Article (Scientific journals)
Stereo-selective cardiac toxicity induced by metconazole via oxidative stress and the wnt/β-catenin signaling pathway in zebrafish embryos
Liu, Lulu; Wang, Fengzhong; Zhang, Zhong et al.
2024In Environmental Pollution, 350
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Keywords :
cis-Metconazole; Oxidative stress; Stereoselective cardiotoxicity; Wnt/β-catenin signaling pathway; Zebrafish; Animals; Cardiotoxicity; Embryo, Nonmammalian; Fungicides, Industrial; Heart; Oxidative Stress; Triazoles; Water Pollutants, Chemical; Wnt Signaling Pathway; Cell death; Defects; Fungicides; Genes; Plants (botany); Stereoselectivity; ataxin 2; beta catenin; caspase 3; chemical compound; homeobox protein Nkx-2.5; malonaldehyde; metconazole; reactive oxygen metabolite; transcription factor GATA 4; transcription factor TBX5; unclassified drug; fungicide; triazole derivative; Catenin signaling; Cis-metconazole; Non-target organism; Signalling pathways; Stereo-selective; β-catenin; concentration (composition); cyprinid; embryo; oxidative stress; toxicity; animal experiment; apoptosis; aquaculture; Article; cardiotoxicity; cis isomer; controlled study; developmental gene; edema; enzyme activity; fluorescence microscopy; gene expression; heart rate; high throughput sequencing; histopathology; nonhuman; pericardium; protein expression; real time polymerase chain reaction; signal transduction; stereoselectivity; transgenic zebrafish; Western blotting; Wnt signaling; zebra fish; animal; drug effect; etiology; heart; nonmammalian embryo; water pollutant; Toxicity
Abstract :
[en] Metconazole (MEZ), a chiral triazole fungicide, produces enantioselective adverse effects in non-target organisms. Among MEZ's isomers, cis-MEZ displays robust antimicrobial properties. Evaluating MEZ and cis-MEZ's toxicity may mitigate fungicide usage and safeguard non-target organisms. Our study evaluated the toxicity of MEZ and its cis-isomers at concentrations of 0.02, 0.2, 2, and 4 mg L−1. We report stereoselectivity and severe cardiovascular defects in zebrafish, including pericardial oedema, decreased heart rate, increased sinus venous and bulbous arteries distances, intersegmental vessel defects, and altered cardiovascular development genes (hand2, gata4, nkx2.5, tbx5, vmhc, amhc, dll4, vegfaa, and vegfc). Further, MEZ significantly increased oxidative stress and apoptosis in zebrafish, primarily in the cardiac region. Isoquercetin, an antioxidant found in plants, partially mitigates MEZ-induced cardiac defects. Furthermore, MEZ upregulated the Wnt/β-catenin pathway genes (wnt3, β-catenin, axin2, and gsk-3β) and β-catenin protein expression. Inhibitor of Wnt Response-1 (IWR-1) rescued MEZ-induced cardiotoxicity. Our findings highlight oxidative stress, altered cardiovascular development genes, and upregulated Wnt/β-catenin signaling as contributors to cardiovascular toxicity in response to MEZ and cis-MEZ treatments. Importantly, 1R,5S-MEZ exhibited greater cardiotoxicity than 1S,5R-MEZ. Thus, our study provides a comprehensive understanding of cis-MEZ's cardiovascular toxicity in aquatic life. © 2024 Elsevier Ltd
Disciplines :
Entomology & pest control
Author, co-author :
Liu, Lulu;  Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China ; Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, Engineering Research Center of High Value Utilization of Western Fruit Resources, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Shaanxi, Xi'an, 710119, China
Wang, Fengzhong;  Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China
Zhang, Zhong;  Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, Engineering Research Center of High Value Utilization of Western Fruit Resources, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Shaanxi, Xi'an, 710119, China
Fan, Bei;  Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China
Luo, Ying;  Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, Engineering Research Center of High Value Utilization of Western Fruit Resources, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Shaanxi, Xi'an, 710119, China
Li, Ling ;  Université de Liège - ULiège > TERRA Research Centre ; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China
Zhang, Yifan;  Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China
Yan, Zhihui;  Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China
Kong, Zhiqiang;  State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Francis, Frédéric  ;  Université de Liège - ULiège > TERRA Research Centre > Gestion durable des bio-agresseurs
Li, Minmin;  Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, China
Language :
English
Title :
Stereo-selective cardiac toxicity induced by metconazole via oxidative stress and the wnt/β-catenin signaling pathway in zebrafish embryos
Publication date :
01 June 2024
Journal title :
Environmental Pollution
ISSN :
0269-7491
eISSN :
1873-6424
Publisher :
Elsevier Ltd
Volume :
350
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 20 March 2025

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