Shvedova-AA; Kisin-ER; Murray-AR; Gorelik-O; Arepalli-S; Castranova-V; Young-SH; Gao-F; Tyurina-YY; Oury-T; Kagan-VE
Toxicol Appl Pharmacol 2007 Jun; 221(3):339-348
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.
Bronchial-asthma; Metal-compounds; Respirable-dust; Particulate-dust; Alveolar-cells; Animal-studies; Vitamins; Antioxidants; Respiratory-system-disorders; Pulmonary-system-disorders; Fibrogenesis; Nanotechnology
Toxicology and Applied Pharmacology
University of Pittsburgh at Pittsburgh