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Cardiovascular Toxicity of Different Sizes Amorphous Silica Nanoparticles in Rats After Intratracheal Instillation

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The purpose of this work was to investigate the cardiovascular toxicity of different sizes and different dosages of silica nanoparticles in Wistar rats. The three silica nanoparticles (30, 60, and 90 nm) and one fine silica particles (600 nm) at three doses of 2, 5, and 10 (mg/Kg bw) were used in the present experiment. After intratracheal instillation for a total of 16 times, concentration of Si in hearts and serum was measured by inductively coupled plasma optical emission spectrometer. The hematology parameters were analyzed by an automated hematology analyzer, and the inflammatory reaction, oxidative stress, endothelial dysfunction, and the myocardial enzymes in serum were measured by kits. Our results showed intratracheal-instilled silica nanoparticles could pass through the alveolar-capillary barrier into systemic circulation. Concentration of Si in the heart and serum depended on the particles size and dosage. The levels of reactive oxygen species (ROS) at 5, 10 mg/Kg bw of the three silica nanoparticles were higher than the fine silica particles. Blood levels of inflammation-related high-sensitivity C-reactive protein and cytokines such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha were increased after exposure to three silica nanoparticles at 10 mg/Kg bw. Moreover, the levels of IL-1β and IL-6 at 10 mg/Kg bw of silica nanoparticles (30 nm) were higher than the fine silica particles. Significant decrease in superoxide dismutase, glutathione peroxidase and significant increase in malondialdehyde were observed at 10 mg/Kg bw of the three silica nanoparticles. A significant decrease in nitric oxide (NO) production was induced which coincided with the reduction of nitric oxide synthase (NOS) activity and the excessive generation of ROS in rats. The levels of intercellular adhesion molecule-l and vascular cell adhesion molecule-l elevated significantly after exposure to three silica nanoparticles at 10 mg/Kg bw, which are considered as early steps of endothelial dysfunction. We conclude that cardiovascular toxicity of silica nanoparticles could be related to the particles size and dosage. Oxidative stress could be involved in inflammatory reaction and endothelial dysfunction, all of which could aggravate cardiovascular toxicology. In addition, endothelial NO/NOS system disorder caused by nanoparticles could be one of the mechanisms for endothelial dysfunction.

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Acknowledgments

The authors would like to thank Prof. Wensheng Yang, and Dr. Jianquan Xu from Jilin University for the preparation of silica particles. This work was supported by Grant of Specialized Research Fund for the Doctoral Program of Higher Education (20090061110062) and Jilin University Research Foundation for Basic Science (200903112).

Conflict of interest

The authors declare that there are no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Jilin University, Changchun, 130021, Jilin, People’s Republic of China

    Zhongjun Du, Dali Zhao, Minghua Jin, Yang Li, Xiaomei Liu, Ying Liu, Haiying Du & Zhiwei Sun

  2. Respiratory Department, The China-Japan Union Hospital, Jilin University, Changchun, 130033, Jilin, People’s Republic of China

    Guanqun Cui

  3. School of Public Health and Family Medicine, Capital Medical University, Beijing, 100069, People’s Republic of China

    Li Jing, Caixia Guo, Xianqing Zhou & Zhiwei Sun

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  1. Zhongjun Du
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Correspondence to Xianqing Zhou or Zhiwei Sun.

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Du, Z., Zhao, D., Jing, L. et al. Cardiovascular Toxicity of Different Sizes Amorphous Silica Nanoparticles in Rats After Intratracheal Instillation. Cardiovasc Toxicol 13, 194–207 (2013). https://doi.org/10.1007/s12012-013-9198-y

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