Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming 650091, China.
Environ Sci Technol. 2022 May 17;56(10):6548-6559. doi: 10.1021/acs.est.2c00973. Epub 2022 May 5.
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.
慢性暴露于微囊藻毒素（MCs）的健康风险（MCs 是一类主要由蓝藻产生的水生污染物）是一个至关重要但尚未解决的问题。尽管有一些流行病学研究，但暴露于 MCs 的人类的代谢谱仍然未知，这阻碍了对分子毒性机制的深入理解。在这里，应用了灵敏的基于核磁共振（NMR）和液相色谱-质谱（LC-MS）的代谢组学方法来研究生活在 Chao 湖附近的人类的血清代谢谱，该湖每年都会发生有毒蓝藻水华。超高效液相色谱-串联质谱（UPLC-MS/MS）检测到 144 份血清中有 92 份含有 MCs，其中位数浓度为 0.016 μg/L。估计的每日摄入量（0.15-0.27 μg MC-LReq/天）低于世界卫生组织（WHO）推荐的可耐受每日摄入量（TDI，60 公斤成人 2.4 μg MC-LR）。证实了氨基酸代谢的明显紊乱，并且在与血清 MC 负荷相关的肾功能损害中发挥了重要作用。慢性经口暴露于 30 μg MC-LR/kg 体重的小鼠，低于无观察到不良效应水平，也导致明显的肾脏损伤和代谢功能障碍。这些观察结果提供了人类暴露于 MCs 时代谢紊乱的第一个证据，并表明 WHO 传统上确定的 TDI 值应降低，以有效地保护人类健康。
