Health Risks of Chronic Exposure to Small Doses of Microcystins: AnIntegrative Metabolomic and Biochemical Study of Human Serum br

Health risks of chronic exposure to microcystins(MCs), a family of aquatic contaminants produced mainly bycyanobacteria, are critical yet unsolved problems. Despite a fewepidemiological studies, the metabolic profiles of humans exposedto MCs remain unknown, hindering the deep understanding of themolecular toxicity mechanisms. Here, sensitive nuclear magneticresonance (NMR)- and liquid chromatography-mass spectrometry(LC-MS)-based metabolomics were applied to investigate theserum metabolic profiles of humans living near Lake Chao, wheretoxic cyanobacterial blooms occur annually. MCs were positivelydetected in 92 of 144 sera by ultra-high-pressure liquidchromatography-tandem mass spectrometry (UPLC-MS/MS)with a median concentration of 0.016 mu g/L. The estimated dailyintake (0.15-0.27 mu g MC-LReq/day) was less than the tolerable daily intake (TDI, 2.4 mu g MC-LR for 60 kg adults) recommendedby the World Health Organization (WHO). Obvious disruptions of the amino acid metabolism were confirmed and playedimportant roles in renal impairments associated with serum MC burdens. Chronic oral exposure of mice to 30 mu g MC-LR/kg bodymass, which is less than the no observed adverse effect level, also led to obvious renal lesions and metabolic dysfunction. Theseobservations provide thefirst evidence of metabolic disturbance of humans exposed to MCs and indicate that the WHO's TDI valuedetermined traditionally should be lessened to protect human health effectively.