PMID- 30538461 OWN - NLM STAT- MEDLINE DCOM- 20190107 LR - 20220330 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 13 DP - 2018 TI - Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system. PG - 7819-7834 LID - 10.2147/IJN.S185259 [doi] AB - BACKGROUND: The harmful effects following the release of nanomaterials into environment are of great concern today. PURPOSE: In this study, subacute effect due to co-exposure to low-dose silica nanoparticles (SiNPs) and lead acetate (Pb) on cardiovascular system was detected in Sprague Dawley male rats. MATERIALS AND METHODS: Histopathological and ultrastructural changes of heart, aortic arch and abdominal aorta were detected. Blood routine and blood biochemistry examinations were used to show the changes of blood components. The fibrinolytic and plasmin factors, inflammation-related factors and myocardial-related enzyme in serum were analysised by ELISA and Western blot assay. RESULTS: Histopathological and ultrastructural examination of heart, aortic arch, and abdominal aorta showed that serious damage occurred in co-exposure group (n=6/group). Blood routine examination showed that leukocytosis and thrombocytopenia increased markedly, while changes in the erythrocyte count were not obvious in the co-exposure group. The expression of alanine transaminase (ALT) decreased obviously in co-exposure group, while no significant changes were noted in the expression of aspartate aminotransferase (AST), cholesterol (CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the co-exposure group on blood biochemistry analysis. In addition, data from ELISA analysis showed that the levels of fibrinolytic and plasmin factors, including thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), tissue-type plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and antithrombin III (AT III), were decreased, while those of human fibrinogen (FIB) and D-dimer (D2D) increased significantly in the co-exposure group. Moreover, the myocardial-related enzyme in serum, tested by ELISA, and cardiovascular-related protein expression of atrial natriuretic peptide and brain natriuretic peptide, tested by Western blot assay, was increased in the heart. Furthermore, the expression of inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) was increased in heart tissue subjected to combined exposure, which was manifested by Western blot assay, while the protein levels of angiotensin II (ANG II) and endothelin 1 were (ET-1) elevated in blood vessels in the co-exposure group. CONCLUSION: In conclusion, the major interactions involved in subacute toxicity due to co-exposure to low doses of SiNPs and Pb on cardiovascular system were expected to be additive and synergistic in nature. Co-exposure to SiNPs and Pb could aggravate the cardiovascular toxicity via endothelial damage, hypercoagulation, and cardiac injury in vivo. FAU - Feng, Lin AU - Feng L AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. FAU - Yang, Xiaozhe AU - Yang X AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. FAU - Shi, Yanfeng AU - Shi Y AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. FAU - Liang, Shuang AU - Liang S AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. FAU - Zhao, Tong AU - Zhao T AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. FAU - Duan, Junchao AU - Duan J AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. FAU - Sun, Zhiwei AU - Sun Z AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China, jcduan@ccmu.edu.cn; zwsun@ccmu.edu.cn. LA - eng PT - Journal Article DEP - 20181121 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Organometallic Compounds) RN - 0 (Proteins) RN - 7631-86-9 (Silicon Dioxide) RN - RX077P88RY (lead acetate) SB - IM MH - Animals MH - Aorta, Abdominal/drug effects/pathology MH - Blood Coagulation/drug effects MH - Cardiovascular System/*drug effects/pathology MH - Male MH - Myocardium/ultrastructure MH - Nanoparticles/*toxicity/ultrastructure MH - Organometallic Compounds/*toxicity MH - Proteins/metabolism MH - Rats, Sprague-Dawley MH - Silicon Dioxide/*toxicity MH - *Toxicity Tests, Acute PMC - PMC6257131 OTO - NOTNLM OT - Pb OT - SiNPs OT - cardiovascular toxicity OT - combined exposure OT - in vivo COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/12/13 06:00 MHDA- 2019/01/08 06:00 PMCR- 2018/11/21 CRDT- 2018/12/13 06:00 PHST- 2018/12/13 06:00 [entrez] PHST- 2018/12/13 06:00 [pubmed] PHST- 2019/01/08 06:00 [medline] PHST- 2018/11/21 00:00 [pmc-release] AID - ijn-13-7819 [pii] AID - 10.2147/IJN.S185259 [doi] PST - epublish SO - Int J Nanomedicine. 2018 Nov 21;13:7819-7834. doi: 10.2147/IJN.S185259. eCollection 2018.