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Chronic exposure to MC-LR increases the risks of microcytic anemia: Evidence from human and mice
Chun Pan1, Minghao Yan1, Haibo Jin1
1Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China.
Abstract:
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 MC-LR 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.
Insights
Microcystins (MCs), potent cyanobacteria toxins, are linked to microcytic anemia in humans. This study reveals MCs disrupt iron homeostasis and erythropoiesis, impacting public health.
Area of Science:
- Environmental Toxicology
- Hematology
- Public Health
Background:
- Microcystins (MCs) from cyanobacteria are potent toxins with largely unknown human health effects.
- Understanding MCs' impact on hematological parameters is crucial for public health.
- Previous research has not fully elucidated the mechanisms of MC toxicity in humans.
Purpose of the Study:
- To investigate the role of Microcystins (MCs) in the development of hematological abnormalities.
- To explore the underlying mechanisms of MC-induced anemia in both human populations and animal models.
- To identify the specific signaling pathways involved in MC toxicity.
Main Methods:
- A case-control study was conducted in Nanjing to assess the association between MC-LR exposure and anemia.
- A chronic mouse model was utilized to study the effects of MC-LR on hematological parameters and related biological pathways.
- Analysis included serum MC-LR levels, complete blood counts, and molecular analysis of key proteins and signaling pathways (e.g., EPO/EPOR, hepcidin, iron homeostasis markers).
Main Results:
- MC-LR exposure was significantly associated with an increased risk of anemia (OR=4.954).
- A negative correlation was observed between serum MC-LR and hemoglobin, hematocrit, MCV, and RBC count.
- Animal models confirmed MC-LR induces microcytic anemia linked to inflammation, iron dysregulation, and impaired erythropoiesis via the EPO/EPOR pathway.
Conclusions:
- Prolonged environmental exposure to Microcystins (MCs) is a probable contributor to human microcytic anemia.
- MCs disrupt erythropoiesis and iron homeostasis, highlighting their significant public health risk.
- This study provides novel insights into the toxicity of MCs and their impact on hematological health.
