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Titanium dioxide induced inflammation in the small intestine

World Journal of Gastroenterology 2012年第34期18卷 4729-4735页

作者： Carolina Maciel Nogueira Walter Mendes de Azevedo maria Lucia Zaidan Dagli Sérgio Hiroshi Toma AndréZonetti de Arruda Leite maria Laura Lordello Iêda Nishitokukado Carmen Lúcia Ortiz-Agostinho maria irmaseixas duarte Marcelo Alves Ferreira Aytan Miranda Sipahi Department of Gastroenterology Laboratory of Clinical and Experimental Gastroen-terologySchool of MedicineUniversity of So PauloCerqueira César01246-900 So PauloBrazil Department of Fundamental Chemistry Federal University of PernambucoCidade Universitária50670-901 RecifeBrazil Department of Pathology Veterinary Medicine SchoolUniversity of So PauloCidade Universitária05508-270 So PauloBrazil Laboratory of Supramolecular Chemistry and Nanotechnology Chemistry InstituteUniversity of So PauloCidade Universitária05513-970 So PauloBrazil Laboratory of Transmissible Disease Medicine SchoolUniversity of So PauloCerqueira César01246-900 So PauloBrazil Laboratory of Cellular Biology Medicine SchoolUniversity of So PauloCerqueira César01246-900 So PauloBrazil

AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ±

关键词： Titanium dioxide Microparticles Nanopar-tides Immune response Small intestine Mice

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