Wang Yaqi, Zhou Xiaodie, Yang Yue, Liu Jun, Yang Fei
Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Cell Biology and Genetics, Institute of Cytology and Genetics, Key Laboratory of Hengyang City on Biological Toxicology and Ecological Restoration, Key Laboratory of Hengyang City on Ecological Impedance Technology of Heavy Metal Pollution in Cultivated Soil of Nonferrous Metal Mining Area, Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education, School of Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Environ Int. 2025 Jul;201:109547. doi: 10.1016/j.envint.2025.109547. Epub 2025 May 29.
Global warming and eutrophication of water bodies have exacerbated the occurrence of cyanobacterial blooms in recent years. Microcystin-LR (MC-LR) produced by cyanobacterial blooms is present in water bodies. Humans and livestock are at significant risk of exposure to MC-LR through drinking water, consuming contaminated food, or inhalation of aerosols containing MC-LR. This article systematically summarizes the formation, fate, and distribution of MC-LR in the body, and explores its toxic effects and mechanisms on the multiple organs containing intestines, liver and kidneys. The study comparatively elucidated MC-LR exerted toxicity including abnormal cell proliferation, inflammation and fibrosis primarily through the following classical mechanisms: (1) inhibiting protein phosphatase 2A (PP2A), thereby affecting signaling pathways such as JNK/P38, MAPK/ERK, and PI3K/AKT; (2) inducing oxidative stress. Additionally, we summarized new mechanisms: (1) MC-LR affects mitophagy or induces mitochondrial structure damage; (2) MC-LR can induce intestinal microbiota dysbiosis, which in turn causes liver and kidney damage via the "gut-liver" axis and "gut-kidney" axis. This study presents the first systematic analysis of the multi-organ toxic effects induced by MC-LR, elucidates potential specific and shared toxic mechanistic pathways and proposes some future research directions to mitigate MC-LR-associated health risks.
近年来，全球变暖和水体富营养化加剧了蓝藻水华的发生。蓝藻水华产生的微囊藻毒素-LR（MC-LR）存在于水体中。人类和牲畜通过饮用水、食用受污染的食物或吸入含有MC-LR的气溶胶，面临着接触MC-LR的重大风险。本文系统总结了MC-LR在体内的形成、归宿和分布，并探讨了其对包括肠道、肝脏和肾脏在内的多个器官的毒性作用及机制。该研究比较阐明了MC-LR主要通过以下经典机制发挥毒性作用，包括异常细胞增殖、炎症和纤维化：（1）抑制蛋白磷酸酶2A（PP2A），从而影响JNK/P38、MAPK/ERK和PI3K/AKT等信号通路；（2）诱导氧化应激。此外，我们总结了新的机制：（1）MC-LR影响线粒体自噬或诱导线粒体结构损伤；（2）MC-LR可诱导肠道微生物群失调，进而通过“肠-肝”轴和“肠-肾”轴导致肝脏和肾脏损伤。本研究首次对MC-LR诱导的多器官毒性作用进行了系统分析，阐明了潜在的特异性和共同的毒性机制途径，并提出了一些未来的研究方向，以降低与MC-LR相关的健康风险。
