Suppression of basal and carbon nanotube-induced oxidative stress, inflammation and fibrosis in mouse lungs by Nrf2

Details

• Personal Author:
  Dong J ; Ma Q
• Description:
  The lungs are susceptible to oxidative damage by inhaled pathogenic agents, including multiwalled carbon nanotubes (MWCNT). The nuclear factor erythroid 2-related factor 2 (Nrf2) has been implicated in regulating the body's defense against oxidative stress. Here, we analyzed the function of Nrf2 in the lungs. Under a basal condition, Nrf2 knockout (KO) mice showed apparent pulmonary infiltration of granulocytes, macrophages and B and T lymphocytes, and elevated deposition of collagen fibers. Exposure to MWCNT (XNRI MWNT-7, Mitsui, Tokyo, Japan) by pharyngeal aspiration elicited rapid inflammatory and fibrotic responses in a dose (0, 5, 20 and 40 mg) and time (1, 3, 7 and 14 d)-dependent manner. The responses reached peak levels on day 7 post-exposure to 40 mg MWCNT, evidenced by massive inflammatory infiltration and formation of inflammatory and fibrotic foci, which were more evident in Nrf2 KO than wildtype (WT) lungs. At the molecular level, Nrf2 protein was detected at a low level under a basal condition, and was dramatically increased by MWCNT in WT, but not Nrf2 KO, lungs. Activation of Nrf2 was inversely correlated with induced expression of fibrosis marker genes and profibrotic cytokines. Furthermore, the levels of ROS and oxidative stress were remarkably higher in Nrf2 KO than WT lungs under a physiological condition, and were dramatically increased by MWCNT, with the increase significantly more striking in KO lungs. The findings reveal that Nrf2 plays an important role in suppressing the basal and MWCNT-induced oxidant production, inflammation and fibrosis in the lungs, thereby protecting against MWCNT lung toxicity. [Description provided by NIOSH]
• Subjects:
  Animals Fibrosis Irritants Laboratories Lung Lung Diseases Occupational Health Pathology Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Author Keywords: Lung Fibrosis Exposure-levels Laboratory-animals Lung-fibrosis Lung-function Lung-tissue Lung Inflammation Multi-walled Carbon Nanotubes Nanotechnology Nanotoxicity Nuclear Factor Erythroid 2-related Factor 2 Oxidative Stress Physiological-effects Proteins Pulmonary-disorders Pulmonary-system Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders Risk-factors

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• ISSN:
  1743-5390
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  10
• Issue:
  6
• NIOSHTIC Number:
  nn:20047109
• Citation:
  Nanotoxicology 2016 Aug; 10(6):699-709
• Contact Point Address:
  Qiang Ma, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Mailstop 3014, 1095 Willowdale Road, Morgantown, WV, USA
• Email:
  qam1@cdc.gov
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Nanotoxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2312cceb5f6c42a0aafa0cbeb401f20a21413226250f7063f0ae719031c1e8eecda21b7efb0a3ec4b0d0ae53fcd13d124dfd8f7edeb0689fb4c40221d62ca283
• Download URL:
  https://stacks.cdc.gov/view/cdc/202301/cdc_202301_DS1.pdf
• File Type:
  [PDF - 3.15 MB ]