Oxidative lipidomics reveals selective, but not random, pulmonary phosphilipid peroxidation after inhalation of carbon nanotubes.
Tyurina-Y; Tyurin-V; Sparvero-L; Amoscato-A; Kapralova-V; Kisin-E; Murray-A; Shi-J; Fadeel-B; Shvedova-A; Kagan-V
Toxicologist 2011 Mar; 120(Suppl 2):252
It is commonly accepted that lipid peroxidation is a mechanism of cell/tissue damage and death by nanoparticles, including single walled carbon nanotubes (SWCNT).We performed global ipidomics/oxidative lipidomics analysis of all molecular species in major classes of phospholipids and established that random free radical peroxidation does not happen in the lung of mice at 3 different time-points after SWCNT inhalation. C57BL/6 mice were exposed to SWCNT via inhalation (5mg/m3, whole body inhalation for 4 consecutive days, 5 h/day) and scarified 1, 7 and 28 days thereafter.We found that two most abundant and susceptible phospholipids - phosphatidylcholine and phosphatidylethanolamine - that constitute more than 75% of total phospholipids, do not undergo peroxidation at all. In addition, we demonstrated that three relatively minor anionic phospholipids - cardiolipin, phosphatidylinositol, and phosphatidylserine get oxidized in a very selective way: only few molecular species out of many in each class (10 out of 25 for CL, 3 out of 5 for PI, 1 out of 7 for PS) were converted into oxygenated species. Moreover, the selectivity was also detected towards fatty acids of the respective oxidized anionic phospholipids (not most polyunsaturated fatty acids but most abundant). We speculate that SWCNT-induced phospholipid peroxidation in lung is involved in the production of selective precursors of pro-resolving mediators of inflammation rather than in non-specific oxidative damage.
Cell-damage; Cell-function; Cellular-reactions; Environmental-control; Injury-prevention; Laboratory-animals; Laboratory-testing; Lung-irritants; Molecular-biology; Molecular-structure; Nanotechnology; Oxidative-metabolism; Oxidative-processes; Peroxidases; Pulmonary-function; Pulmonary-system; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis; Tissue-disorders; Toxins
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
University of Pittsburgh at Pittsburgh