title: Inflammatory response and blood hypercoagulable state induced by low level co-exposure with silica nanoparticles and benzo[a]pyrene in zebrafish (Danio rerio) embryos.
abstract: 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.
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China. Electronic address: jcduan@ccmu.edu.cn.
authors.forename: Junchao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry, Renmin University of China, Beijing, PR China.
authors.forename: Yapei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China. Electronic address: zwsun@ccmu.edu.cn.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects; D004347:Drug Interactions; D004487:Edema / Q000139:chemically induced; D004625:Embryo, Nonmammalian; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D053758:Nanoparticles / Q000633:toxicity*; D010496:Pericardium / Q000187:drug effects / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015027:Zebrafish / Q000097:blood / Q000378:metabolism
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D001564:Benzo(a)pyrene; D012822:Silicon Dioxide
keywords: Benzo[a]pyrene; Blood hypercoagulable state; Co-exposure; Inflammatory response; Silica nanoparticles; Zebrafish