TY - JOUR
T1 - Health Risks of Chronic Exposure to Small Doses of Microcystins
T2 - An Integrative Metabolomic and Biochemical Study of Human Serum
AU - He, Jun
AU - Chen, Jun
AU - Chen, Feng
AU - Chen, Liang
AU - Giesy, John P.
AU - Guo, Yuming
AU - Liang, Gaodao
AU - Deng, Xuwei
AU - Wang, Wenjing
AU - Xie, Ping
N1 - Funding Information:
This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB31000000); the National Natural Science Foundation of China (grant nos 31770555 and 31600423); and the State Key Laboratory of Freshwater Ecology and Biotechnology (2019FBZ03).
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/5/17
Y1 - 2022/5/17
N2 - 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.
AB - 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.
KW - epidemiological study
KW - health risk
KW - metabolomics
KW - microcystin
KW - renal injury
UR - http://www.scopus.com/inward/record.url?scp=85130046727&partnerID=8YFLogxK
U2 - 10.1021/acs.est.2c00973
DO - 10.1021/acs.est.2c00973
M3 - Article
C2 - 35510355
AN - SCOPUS:85130046727
SN - 0013-936X
SP - 6548
EP - 6559
JO - Environmental Science and Technology
JF - Environmental Science and Technology
ER -