Biological Trace Element Research

, Volume 140, Issue 2, pp 186–197 | Cite as

P38-Nrf-2 Signaling Pathway of Oxidative Stress in Mice Caused by Nanoparticulate TiO2

  • Jue Wang
  • Na Li
  • Lei Zheng
  • Sisi Wang
  • Ying Wang
  • Xiaoyang Zhao
  • Yanmei Duan
  • Yaling Cui
  • Min Zhou
  • Jingwei Cai
  • Songjie Gong
  • Han Wang
  • Fashui Hong


Some recent studies have been previously suggested that nanoparticulate titanium dioxide (TiO2) damaged liver function and decreased immunity of mice, but the spleen injury and its oxidative stress mechanism are still unclear. To understand the spleen injury induced by intragastric administration of nanoparticulate anatase TiO2 for consecutive 30 days, the spleen pathological changes, the oxidative stress, and p38 and c-Jun N-terminal kinase signaling pathways, along with nuclear factor-κB and nuclear factor-E2-related factor-2 (Nrf-2), were investigated as the upstream events of oxidative stress in the mouse spleen from exposure to nanoparticulate TiO2. The results suggested that nanoparticulate TiO2 caused congestion and lymph nodule proliferation of spleen tissue, which might exert its toxicity through oxidative stress, as it caused significant increases in the mouse spleen reactive oxygen species accumulations, subsequently leading to the strong lipid peroxidation and the significant expression of heme oxygenase-1 via the p38-Nrf-2 signaling pathway. The studies on the mechanism by which nanoparticulate TiO2 induced the p38-Nrf-2 signaling pathway are helpful to a better understanding of the nanoparticulate TiO2-induced oxidative stress and reduction of immune capacity.


Nanoparticulate TiO2 Spleen Oxidative stress p38 MAP kinases Nuclear factor-E2-related factor-2 Heme oxygenase-1 



This work was supported by the National Natural Science Foundation of China (grant no. 30901218), the Medical Development Foundation of Soochow University (grant no. EE120701, China), the National Bringing New Ideas Foundation of Student of China (grant nos. 57315427, 57315927), and the Bringing New Ideas Foundation of Postgraduate of Medical College of Soochow University (China) and the Soochow University Start-up Fund (grant no. Q4134918, China).


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jue Wang
    • 1
  • Na Li
    • 1
  • Lei Zheng
    • 1
  • Sisi Wang
    • 1
  • Ying Wang
    • 1
  • Xiaoyang Zhao
    • 1
  • Yanmei Duan
    • 1
  • Yaling Cui
    • 1
  • Min Zhou
    • 1
  • Jingwei Cai
    • 1
  • Songjie Gong
    • 1
  • Han Wang
    • 1
  • Fashui Hong
    • 1
  1. 1.Medical CollegeSoochow UniversitySuzhouPeople’s Republic of China

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