Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system

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 coexposure 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.