Effects of Multi-Walled Carbon Nanotube Exposure on Brain Oxidative Stress and Inflammation in C57BL/6 Mice

Details

• Personal Author:
  Begay J ; Campen M ; Erdely A ; Herbert G ; Lucas S ; Ottens AK ; Sanchez B ; Young TL
• Description:
  In vivo models demonstrate increased brain and lung inflammatory activation, disrupted blood-brain barrier (BBB) integrity, increased oxidative stress, serum profile changes, impaired endothelial function, and vasodilatory insufficiencies following multi-walled carbon nanotube (MWCNT) exposure. The mechanisms by which lung exposure to MWCNTs mediate neuroinflammation are explored in this study. We hypothesized that the MWCNT exposure induces serum peptide composition modifications that mediate pro-inflammatory and pro-oxidative stress changes in the brain, likely delivered via exosomes. To test this hypothesis, male wild-type C57BL/6 mice (6-8 weeks) exposed to vehicle (dispersion media), 3, 10 or 40 microg MWCNT via oropharyngeal aspiration were euthanized at various time points post exposure. Pulmonary inflammation was assessed via bronchoalveolar lavage fluid (BALF) cell and protein quantification and inflammatory cytokine/chemokine expression was determined by electrochemiluminescence. Serum bioactivity of whole and exosome-depleted fractions was assessed in mouse brain endothelial cells via serum cumulative inflammatory potential (SCIP) assay. Vasodilatory changes were determined via myography. Brain glutathione levels were measured using colorimetric assay to evaluate brain oxidative stress changes. Neuroinflammation and BBB changes were assessed via immunofluorescence staining. MWCNT exposure significantly increased macrophage and neutrophil infiltration in BALF. Cytokines (IL-1beta, IL-4, IL-5, TNF-alpha and KC/GRO) were elevated in the BALF of MWCNT-exposed mice. Brain immunofluorescent staining revealed increased albumin staining in extravascular spaces of exposed mice compared to controls. Studies to evaluate oxidative stress, neuroinflammation and exosomal contributions are ongoing. These preliminary findings suggest that MWCNT exposure induced a pro-inflammatory milieu that may disrupt the BBB. [Description provided by NIOSH]
• Subjects:
  Albumins Biological Assay Blood Environmental Exposure Immune System Laboratories Lung Macrophages Nervous System Occupational Health Respiratory System Safety Toxicology

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• Keywords:
  Albumin Alveolar Cells Bioactivation Bioassays Blood Stream Blood Vessels Brain Damage Brain Function Brain Matter Carbon Nanotubes Cell Function Cellular Effects Cellular Reactions CNT Cytokines Dose Response Electrochemical Reactions Exposomes Exposure Assessment Exposure Levels Gene Expression Immune Reaction In Vivo Study Laboratory Animals Laboratory Testing Luminescence Lung Cells Multi-walled Carbon Nanotubes MWCNT Nanotoxicology Nanotubes Neurological System Neurotoxic Effects Neutrophils Oxidative Stress Peptides Proteins Pulmonary Effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; New Mexico ; OSHA Region 3 ; OSHA Region 6 ; Virginia ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  292-293
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20055017
• Citation:
  Toxicologist 2019 Mar; 168(1):292-293
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Glutathione (CAS RN 70-18-8)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center, Albuquerque, New Mexico
• Peer Reviewed:
  False
• Start Date:
  20150930
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• End Date:
  20190929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:831b16e9fecdeaa539a126aee64de01235f1121ee7a6f3a063adc22fb4c8d2cc7ee258dedcc69116564c48cf463da95fa242f897e2dda9a01e96a1d60d8bd4b3
• Download URL:
  https://stacks.cdc.gov/view/cdc/217420/cdc_217420_DS1.pdf
• File Type:
  [PDF - 900.75 KB ]