Inflammatory response and blood hypercoagulable state induced by low level co-exposure with silica nanoparticles and benzo[a]pyrene in zebrafish (Danio rerio) embryos

• Co-exposure of SiNPs and B[a]P induce cardiac toxicity and erythrocyte aggregation.
• Co-exposure of SiNPs and B[a]P trigger the inflammation without ROS generation.
• Co-exposure of SiNPs and B[a]P upregulate the proinflammatory and procoagulant genes.
• Co-exposure of SiNPs and B[a]P activate the TF transcription site, AP-1/c-Jun.

Given the severe situation of world-wide particulate matter air pollution, it is urgent to explore the combined effects of particulate matter components on cardiovascular system. Using zebrafish model, this study was aimed to determine whether the low level co-exposure to silica nanoparticles (SiNPs) and benzo[a]pyrene (B[a]P) had a pronounced cardiovascular toxicity than the single exposure to either SiNPs or B[a]P alone. The FTIR and TGA analysis showed that the co-exposure system possessed of high absorption and thermal stability. Embryos exposed to SiNPs or B[a]P alone did not show cardiac toxicity phenotype at the NOAEL level. However, embryos co-exposed to SiNPs and B[a]P exhibited pericardial edema and bradycardia. While ROS generation remained unaffected, the co-exposure induced significant neutrophil-mediated inflammation and caused erythrocyte aggregation in caudal vein of embryos. Microarray analysis and STC analysis were performed to screen the cardiovascular-related differential expression genes and the expression trend of genes in each group. The co-exposure of SiNPs and B[a]P significantly enhanced the expression of proinflammatory and procoagulant genes. Moreover, the co-exposure markedly increased the phosphorylated AP-1/c-Jun and induced TF expression, but not NF-κB p65. This study for the first time demonstrated the inflammatory response and blood hypercoagulable state were triggered by the combination of SiNPs and B[a]P at low level exposure.

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