The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles.

To understand the chronic spleen injury induced by intragastric administrations with 2.5, 5, and 10 mg kg-1 body weight titanium dioxide nanoparticles (TiO2 NPs) for 90 consecutive days, histopathological and ultrastructure changes, hematological parameters, lymphocyte subsets, the inflammatory, and apoptotic cytokines in the mouse spleen were investigated. Our findings indicate that TiO2 NPs exposure results in the significant increase in the spleen indices, histopathological changes, and splenocyte apoptosis in spleen. Especially, in these TiO2 NPs-treated mice, immunoglobulin, blood cells, platelets, hemoglobin, lymphocyte subsets (such as CD3, CD4, CD8, B cell, natural killer cell) of mice were significantly decreased. Furthermore, TiO2 NPs exposure can significantly increase the levels of nucleic factor-?B, tumor necrosis factor-a, macrophage migration inhibitory factor, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1 beta, cross-reaction protein, transforming growth factor-beta, interferon-?, Bax, and CYP1A1 expression, whereas decrease the levels of Bcl-2 and heat shock protein 70 expression. These findings suggest that long-term exposure to low dose TiO2 NPs may result in spleen injury and reduction of immune capacity, TiO2 NP-induced injury in spleen may result from alteration of inflammatory and apoptotic cytokines expression, and workers and consumers should take great caution when handling nanomaterials. (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.