首页|Titanium dioxide induced inflammation in the small intestine
Titanium dioxide induced inflammation in the small intestine
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AIM:To investigate the effects of titanium dioxide (TiO2)nanoparticles (NPTiO2) and microparticles (MPTiO2)on the inflammatory response in the small intestine of mice.METHODS:BI 57/6 male mice received distilled water suspensions containing TiO2 (100 mg/kg body weight)as NPTiO2 (66 nm),or MPTiO2 (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-IO,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 immunohistochemistry.The titanium content was determined by inductively coupled plasma atomic emission spectrometry.RESULTS:We found increased levels of T CD4+ cells (cells/mm2) 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 TiO2 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); IFNy:NP 15.85± 9.99,MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-α:NP 780.70 ± 318.50,MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05).CONCLUSION:Our findings indicate that TiO2 particles induce a Thl-mediated inflammatory response in the small bowel in mice.
Carolina Maciel Nogueira、Walter Mendes de Azevedo、Maria Lucia Zaidan Dagli、Sérgio Hiroshi Toma、André Zonetti de Arruda Leite、Maria Laura Lordello、I(e)da Nishitokukado
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Department of Gastroenterology, Laboratory of Clinical and Experimental Gastroenterology, School of Medicine, University of S(ā)o Paulo, Cerqueira César, 01246-900 S(ā)o Paulo, Brazil
Department of Fundamental Chemistry, Federal University of Pernambuco, Cidade Universitária,50670-901 Recife, Brazil
Department of Pathology, Veterinary Medicine School, University of S(ā)o Paulo, Cidade Universitária,05508-270 S(ā)o Paulo, Brazil
Laboratory of Supramolecular Chemistry and Nanotechnology, Chemistry Institute, University of S(ā)o Paulo, Cidade Universitária, 05513-970 S(ā)o Paulo, Brazil