Vitamin E Deficiency Enhances Pulmonary Inflammatory Response and Oxidative Stress Induced by Single Walled Carbon Nanotubes in C57BL/6 Mice
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2007/03/01
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Personal Author:Arepalli S ; Castranova, Vincent ; Gao F ; Gorelik O ; Kagan VE ; Kisin ER ; Murray AR ; Oury T ; Shvedova AA ; Tyurina YY ; Young SH
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Description:Exposure of mice to single walled carbon nanotubes (SWCNT) induces an unusually robust pulmonary inflammatory response with a very early onset of fibrosis, which is accompanied by a significant oxidative stress and antioxidant depletion. The role of specific components of the antioxidant protective system, specifically vitamin E, the major lipid-soluble antioxidant of membranes and lipoproteins, in the SWCNT induced reactions required further investigation. We used C57BL/6 mice, maintained on a vitamin E-sufficient diet as well as on a vitamin E-deficient diet, to explore and compare the pulmonary inflammatory reactions to aspired SWCNTs. The induced vitamin E-deficiency (a 90-fold depletion of á-tocopherol in the lung) resulted in a significant decline of other antioxidants as well as in accumulation of lipid peroxidation products. A more severe decrease of pulmonary antioxidants was detected in SWCNT treated vitamin E-deficient mice as compared to controls. Exposure of vitamin E-sufficient mice to SWCNTs markedly shifted the ratio of low to high molecular weight forms of extra-cellular SOD (EC-SOD) such that approximately 3-4 times greater amounts of this neutrophil-associated enzyme were present. This effect was enhanced in vitamin E-deficient animals. Lowered levels of antioxidants in vitamin E-deficient mice were associated with a higher sensitivity to SWCNT-induced acute inflammation (PMNs number, released LDH, protein content, pro-inflammatory cytokines level) as well as pro-fibrotic pathways (TGF-â elevation and collagen deposition). Given that pulmonary levels of vitamin E can be manipulated through diet, its effects on SWCNT responses may be of practical importance in optimizing protective anti-inflammatory strategies. [Description provided by NIOSH]
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ISSN:1096-6080
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Pages in Document:37
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Volume:96
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Issue:1
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NIOSHTIC Number:nn:20031895
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Citation:Toxicologist 2007 Mar; 96(1):37
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Federal Fiscal Year:2007
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Performing Organization:University of Pittsburgh at Pittsburgh
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Peer Reviewed:False
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Start Date:20050701
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End Date:20160630
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Main Document Checksum:urn:sha-512:f981cc057980204b3e057cd9973ef7aba48594b8acb7695935175e7f60206f9fa186a70b7bec51e4c837f86a5877dd9354647fa3de8425a641d8590fc9835e7c
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