Department of Cell Biology and Genetics, Institute of Cytology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, 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, University of South China, Hengyang, Hunan 421001, China; School of Public Health, Hengyang Medical School, Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, University of South China, Hengyang, Hunan 421001, China.
Department of Cell Biology and Genetics, Institute of Cytology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, 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, University of South China, Hengyang, Hunan 421001, China; School of Public Health, Hengyang Medical School, Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, University of South China, Hengyang, Hunan 421001, China.
Sci Total Environ. 2023 Dec 20;905:167167. doi: 10.1016/j.scitotenv.2023.167167. Epub 2023 Sep 18.
Microcystins (MCs) are a class of biologically active cyclic heptapeptide pollutants produced by the freshwater alga Microcystis aeruginosa. With increased environmental pollution, MCs have become a popular research topic. In recent years, the hepatotoxicity of MCs and associated effects and mechanisms have been studied extensively. Current epidemiological data indicate that long-term human exposure to MCs can lead to severe liver toxicity, acute toxicity, and death. In addition, current toxicological studies on the liver, a vital target organ of MCs, indicate that MC contamination is associated with the development of liver cancer, nonalcoholic fatty liver, and liver fibrosis. MCs produce hepatotoxicity that affects the metabolic homeostasis of the liver, induces apoptosis, and acts as a pro-cancer factor, leading to liver lesions. MCs mainly mediate the activation of signaling pathways, such as the ERK/JNK/p38 MAPK and IL-6-STAT3 pathways, which leads to oxidative damage and even carcinogenesis. Moreover, MCs can act synergistically with other pollutants to produce combined toxicity. However, few systematic reviews have been performed on these new findings. This review systematically summarizes the toxic effects and mechanisms of MCs on the liver and discusses the combined liver toxicity effects of MCs and other pollutants to provide reference for subsequent research. The toxicity of different MC isomers deserves further study. The detection methods and limit standards of MCs in agricultural and aquatic products will represent important research directions in the future. Standard protocols for fish sampling during harmful algal blooms or to evaluate the degree of MC toxicity in nature are lacking. In future, bioinformatics can be applied to offer insights into MC toxicology research and potential drug development for MC poisoning. Further research is essential to understand the molecular mechanisms of liver function damage in combined-exposure toxicology studies to establish treatment for MC-induced liver damage.
微囊藻毒素（MCs）是一种由淡水蓝藻铜绿微囊藻产生的具有生物活性的环状七肽污染物。随着环境污染的加剧，MCs 已成为一个热门的研究课题。近年来，MCs 的肝毒性及其相关作用和机制已得到广泛研究。目前的流行病学数据表明，人类长期暴露于 MCs 可导致严重的肝毒性、急性毒性和死亡。此外，目前对 MCs 主要靶器官肝脏的毒理学研究表明，MC 污染与肝癌、非酒精性脂肪肝和肝纤维化的发生有关。MCs 产生肝毒性，影响肝脏的代谢稳态，诱导细胞凋亡，并作为致癌因子导致肝损伤。MCs 主要通过激活 ERK/JNK/p38 MAPK 和 IL-6-STAT3 等信号通路来介导肝毒性，导致氧化损伤甚至致癌。此外，MCs 可以与其他污染物协同作用产生联合毒性。然而，针对这些新发现的系统性综述很少。本综述系统总结了 MCs 对肝脏的毒性作用和机制，并讨论了 MCs 与其他污染物的联合肝毒性作用，为后续研究提供参考。不同 MC 异构体的毒性值得进一步研究。MCs 在农产品和水产品中的检测方法和限量标准将是未来的重要研究方向。在有害藻类大量繁殖期间或评估自然界中 MC 毒性程度时，缺乏鱼类采样的标准协议。未来，生物信息学可以应用于 MC 毒理学研究和 MC 中毒潜在药物开发提供思路。在联合暴露毒理学研究中，为了建立 MC 诱导肝损伤的治疗方法，进一步研究肝损伤的分子机制是必要的。
