Chronic exposure to MC-LR increases the risks of microcytic anemia: Evidence from human and mice

Microcystins (MCs) produced by cyanobacteria are potent toxins to humans that cannot be ignored. However, the toxicity of MCs to humans remains largely unknown. The study explored the role of MCs in the development of hematological parameters through human observations and a chronic mouse model to explore related mechanisms. The adjusted odds ratio of MC-LR to the risk of anemia was 4.954 (95 % CI, 2.423-10.131) in a case control study in Nanjing. An inverse correlation between serum MC-LR and hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and red blood cell count (RBC) was observed. MC-LR in the serum of the population was an independent risk factor for microcytic anemia. Animal experiments demonstrated that MCLR resulted in microcytic anemia, which is associated with inflammation, dysregulation of iron homeostasis, and erythropoiesis. We first identified the possible signaling pathway of MC-LR-induced anemia that MC-LR significantly upregulated the levels of hepcidin via EPO/EPOR signaling pathway and the decreased levels of Twsg1 and Gdf15, thereby resulting in the decreased levels of Hbb and Fpn, and the increased expression of Fth1, and Tf in a chronic mouse model. Our study first identified that prolonged environmental exposure to MCs probably contribute to the occurrence of microcytic anemia in humans, which provides new insights into the toxicity of MCs for public health.