Health Risks of Chronic Exposure to Small Doses of Microcystins: An Integrative Metabolomic and Biochemical Study of Human Serum
- Jun He
Jun HeDonghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaMore by Jun He
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- Jun Chen
Jun ChenDonghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaMore by Jun Chen
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- Feng Chen
Feng ChenDonghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaMore by Feng Chen
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- Liang Chen
Liang ChenDonghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaInstitute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming 650091, ChinaMore by Liang Chen
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- John P. Giesy
John P. GiesyToxicology Center, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatoon S7N 5B3, CanadaDepartment of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatoon S7N 5B4, CanadaZoology Department, Institute for Integrative Toxicology, Michigan State University, 1129 Farm Lane Road, East Lansing, Michigan 48824, United StatesDepartment of Environmental Sciences, Baylor University, Waco 76706, Texas, United StatesMore by John P. Giesy
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- Yuming Guo
Yuming GuoSchool of Public Health and Preventive Medicine, Monash University, Melbourne 3004, AustraliaMore by Yuming Guo
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- Gaodao Liang
Gaodao LiangWuhan Centers for Disease Control and Prevention, Wuhan 430072, ChinaMore by Gaodao Liang
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- Xuwei Deng
Xuwei DengDonghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaMore by Xuwei Deng
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- Wenjing Wang
Wenjing WangKey Laboratory of Coastal Zone Environmental Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, ChinaMore by Wenjing Wang
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- Ping Xie*
Ping XieDonghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaInstitute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming 650091, ChinaMore by Ping Xie
Abstract
Health risks of chronic exposure to microcystins (MCs), a family of aquatic contaminants produced mainly by cyanobacteria, are critical yet unsolved problems. Despite a few epidemiological studies, the metabolic profiles of humans exposed to MCs remain unknown, hindering the deep understanding of the molecular toxicity mechanisms. Here, sensitive nuclear magnetic resonance (NMR)- and liquid chromatography–mass spectrometry (LC–MS)-based metabolomics were applied to investigate the serum metabolic profiles of humans living near Lake Chao, where toxic cyanobacterial blooms occur annually. MCs were positively detected in 92 of 144 sera by ultra-high-pressure liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) with a median concentration of 0.016 μg/L. The estimated daily intake (0.15–0.27 μg MC-LReq/day) was less than the tolerable daily intake (TDI, 2.4 μg MC-LR for 60 kg adults) recommended by the World Health Organization (WHO). Obvious disruptions of the amino acid metabolism were confirmed and played important roles in renal impairments associated with serum MC burdens. Chronic oral exposure of mice to 30 μg MC-LR/kg body mass, which is less than the no observed adverse effect level, also led to obvious renal lesions and metabolic dysfunction. These observations provide the first evidence of metabolic disturbance of humans exposed to MCs and indicate that the WHO’s TDI value determined traditionally should be lessened to protect human health effectively.
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