In vivo evidence of free radical formation in the mouse lung and distant organs after exposure to single-walled carbon nanotubes

Details

• Personal Author:
  Kadiiska MB ; Kisin ER ; Murray AR ; Shvedova AA
• Description:
  Previously, we have reported that pharyngeal exposure of C57BL/6 mice to single walled carbon nanotubes (SWCNTs) caused formation of granulomatous bronchial interstitial pneumonia, fibrosis, oxidative stress, acute inflammatory/cytokine responses and a decrease in pulmonary function. In the current study, we used electron spin resonance (ESR) to directly assess whether pulmonary exposure to respirable SWCNTs caused formation of free radicals in the lungs and in two distant organs, the heart and liver. Here we report that exposure to partially purified SWCNTs (HiPco, CNI, Inc, TX) resulted in the augmentation of oxidative stress as evidenced by ESR detection of a-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) spin-trapped carbon-centered lipid-derived radicals recorded shortly after the treatment. This was accompanied by a significant depletion of antioxidants and elevated biomarkers of inflammation presented by recruitment of inflammatory cells and an increase in pro-inflammatory cytokines in the lungs, as well as development of multifocal granulomatous pneumonia, interstitial fibrosis and suppressed pulmonary function. Moreover, pulmonary exposure to SWCNTs also caused the formation of carbon-centered lipid-derived radicals in the heart and liver at later time points (day 7 post exposure). Additionally, SWCNTs induced a significant accumulation of oxidatively modified proteins, an increase in lipid peroxidation products, depletion of antioxidants and an inflammatory response in both the heart and the liver. Overall, we provided direct evidence that lipid-derived free radicals are a critical contributor to tissue damge induced by SWCNTs not only in the lungs, but in distant organs. [Description provided by NIOSH]
• Subjects:
  Antioxidants Biomarkers Environmental Monitoring Fibrosis Free Radicals Immune System Lipids Lung Occupational Health Respiratory System Safety Spectrum Analysis Toxicology

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• Keywords:
  Carbon-compounds Cellular-reactions Exposure-assessment Free-radicals Heart Immune-reaction In-vivo-study Lipid-peroxidation Liver Lung-irritants Nanotechnology Organs Oxidative-enzymes Oxidative-processes Proteins Pulmonary-function Spectrographic-analysis Tissue-disorders

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; North Carolina ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045917
• Citation:
  Toxicologist 2015 Mar; 144(1):265
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; α-(4-Pyridyl-1-oxide)-N-tert-butylnitrone (CAS RN 66893-81-0)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Mining
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:50bba09ba1f84fb74d28d9a89e92afdb591d8936424d04262bcf8607dcab4f625863dd3994b353bc503141fdc31e261056010c22c37d229c5955283512493260
• Download URL:
  https://stacks.cdc.gov/view/cdc/201153/cdc_201153_DS1.pdf
• File Type:
  [PDF - 227.09 KB ]