State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, PR China.
Environ Int. 2020 May;138:105648. doi: 10.1016/j.envint.2020.105648. Epub 2020 Mar 15.
Microcystins (MCs) produced by cyanobacteria pose serious threats to human health. However, the contribution of long-term exposure to MCs to the development of nonalcoholic fatty liver disease (NAFLD) remains poorly documented. In this study, we estimated the environmental uptake of MCs by a small population of fishers who have lived for many years on Meiliang Bay of Lake Taihu, where cyanobacterial blooms occur frequently. Serum biochemical indices of liver function and their relationships with MC contamination in these people were also investigated. Moreover, to mimic the long-term effects of MC on the livers of fishers, an animal model was established in which mice were exposed to MC-LR at an environmentally relevant level, a reference level (the no-observed adverse effect level, NOAEL), and three times the NOAEL through drinking water for 12 months. We estimated the total daily intake of MCs by fishers through contaminated lake water and food to be 5.95 μg MC-LReq, far exceeding the tolerable daily intake (2.40 μg MC-LReq) proposed by the World Health Organization (WHO). More than 80% of participants had at least one abnormal serum marker. The indices of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), triglyceride (TG), globulin (GLB), and lactate dehydrogenase (LDH) had close positive associations with MC contamination, indicating that both liver damage and lipid metabolism dysfunction were induced by chronic MC exposure. Furthermore, the animal experimental results showed that long-term exposure to MC-LR at the environmentally relevant level led to hepatic steatosis with molecular alterations in circadian rhythm regulation, lipid metabolic processes, and the cell cycle pathway. Exposure to MC-LR at or above the NOAEL worsened the pathological phenotype towards nonalcoholic steatohepatitis disease (NASH) or fibrosis. These results suggest that prolonged exposure to the reference level (NOAEL) of MC-LR could cause severe liver injury to mammals. People with long-term environmental exposure to MCs might be at high risk for developing NAFLD.
微囊藻毒素（MCs）由蓝藻产生，对人类健康构成严重威胁。然而，长期暴露于 MCs 对非酒精性脂肪性肝病（NAFLD）的发展的影响仍缺乏记录。在这项研究中，我们评估了长期生活在太湖梅梁湾的少数渔民对 MCs 的环境摄取量，该地区经常发生蓝藻水华。我们还研究了这些人的血清生化肝功能指标及其与 MC 污染的关系。此外，为了模拟 MC 对渔民肝脏的长期影响，我们建立了一个动物模型，通过饮用水让小鼠在环境相关水平（无观察到不良效应水平，NOAEL）和三倍的 NOAEL 下暴露于 MC-LR 长达 12 个月。我们通过受污染的湖水和食物估算渔民的 MC 总日摄入量为 5.95μg MC-LReq，远远超过世界卫生组织（WHO）提出的可耐受日摄入量（2.40μg MC-LReq）。超过 80%的参与者至少有一种异常的血清标志物。天冬氨酸转氨酶（AST）/丙氨酸转氨酶（ALT）、甘油三酯（TG）、球蛋白（GLB）和乳酸脱氢酶（LDH）的指数与 MC 污染密切相关，表明肝损伤和脂质代谢功能障碍均由慢性 MC 暴露引起。此外，动物实验结果表明，长期暴露于环境相关水平的 MC-LR 导致肝脂肪变性，同时还引起了生物钟调节、脂质代谢过程和细胞周期途径的分子改变。暴露于 MC-LR 达到或超过 NOAEL 会使病理表型向非酒精性脂肪性肝炎（NASH）或纤维化恶化。这些结果表明，长期暴露于 MC-LR 的参考水平（NOAEL）可能会对哺乳动物造成严重的肝损伤。长期接触 MC 的人群可能面临患 NAFLD 的高风险。
