Rare earth element lanthanum induces inflammatory response in zebrafish through TLR4/NF-κB signaling pathway

The inflammatory response is a core protective physiological process against stimuli like infection or injury, and can be initiated by autoimmune disorders. It is primarily characterized by neutrophil-dominated leukocytosis and may lead to multiple organ dysfunction in severe cases. Environmental factors play an important role in the inflammatory response. Rare earth elements are not essential elements for living organisms. However, owing to large-scale mining and use, their concentrations in the environment have increased. Thus, rare earth elements are now considered emerging environmental pollutants, and the risks that rare earth elements pose to human health need further investigation. In this study, zebrafish were used as experimental animals, and zebrafish embryos were exposed to the different concentrations of lanthanum chloride (0, 5, 15, and 25 mg/L) to analyze its effect on embryo development and immune system. The number and distribution of zebrafish neutrophils as well as changes in oxidative stress and the expression of genes related to inflammation were analyzed. The results indicated that lanthanum chloride exposure reduced the heart rate, shortened the body length, and increased the yolk area of zebrafish embryos. In addition, exposure to lanthanum chloride caused the diffusion of neutrophils, leading to inflammation in zebrafish. Concurrently, the exposure led to the accumulation of reactive oxygen species in zebrafish, which subsequently resulted in the upregulation of malondialdehyde, catalase, and superoxide dismutase levels. Further experiments revealed that exposure to lanthanum chloride led to the upregulation of several inflammation-related genes, such as IL-6 , IL-8 , IL-10 , and cxcl-c1c , as well as certain TLR4/NF-κB signaling-related genes, including TLR4 , MyD88 , NF-κB P65 , IL-1β , and TNF-α . The TLR4/NF-κB signaling pathway inhibitor andrographolide can alleviate the inflammatory response induced by lanthanum chloride exposure. In conclusion, lanthanum chloride induced inflammation in zebrafish by activating the TLR4/NF-κB signaling pathway. The study results can provide a reference for evaluating the health risks of rare earth elements in humans.