Nanoparticle Inhalation Increases Microvascular Oxidative Stress and Compromises Nitric Oxide Bioavailability

Details

• Personal Author:
  Boegehold M ; Castranova, Vincent ; Chen B ; Dreher K ; Frazer D ; Hubbs A ; Mosely A ; Nurkiewicz TR
• Description:
  We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs are unclear. The purpose of this study was to identify alterations in the production of oxidative stress and endogenous nitric oxide (NO) after nanoparticle exposure, and determine the relative contribution of hemoproteins and oxidative enzymes in this process. Rats were exposed to TiO2 nanoparticles via inhalation (primary particle diameter approximately 21 nm) at depositions of 4-90 mu g/rat. The spinotrapezius muscle was prepared for intravital microscopy 24 hrs after exposures. Intraluminal infusion of the Ca2+ ionophore A23187 was used to evaluate endothelium- dependent arteriolar dilation. Endogenous microvascular NO production was measured with an electrochemical sensor. Oxidative stress in the microvascular wall was quantified via dihydroethidium fluorescence (O2 - probe). Histological sections of pulmonary tissue revealed nanoparticle uptake by alveolar macrophages, and migration to nearby lymph tissue. TiO2 nanoparticles quenched spontaneous NO signals generated in vitro by S-Nitroso-N-acetyl-D,L-penicillamine (550 mM). As in previous experiments, A23187 produced dose-dependent arteriolar dilations (10- 69% of maximum response). Nanoparticle exposure robustly attenuated this to 6- 16% of the maximum response. Nanoparticle exposure also increased microvascular oxidative stress by approximately 60%, and decreased NO production. Inhibition of either myeloperoxidase (4-aminobenzoic hydrazide, 10 um) or NADPH oxidase (apocynin, 10-4 M) partially restored NO production and normal microvascular function. These results indicate that in conjunction with microvascular dysfunction, nanoparticle exposure also increases local oxidative stress and decreases NO bioavailability. [Description provided by NIOSH]
• Subjects:
  Biological Factors Blood Cardiovascular Diseases Cardiovascular System Environmental Monitoring Laboratories Microbiology Musculoskeletal System Occupational Health Oxidants Particulate Matter Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Biological-effects Biological-factors Blood-vessels Cardiovascular-function Cardiovascular-system Cardiovascular-system-disorders Dose-response Electrochemical-analysis Electrochemical-reactions Electrochemistry Exposure-assessment Exposure-levels Exposure-methods Inhalation-studies Laboratory-animals Microscopic-analysis Microscopy Musculoskeletal-system Nanotechnology Oxidative-enzymes Oxidative-metabolism Particulates Pulmonary-system-disorders Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; 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:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035260
• Citation:
  Toxicologist 2009 Mar; 108(1):279
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f9064f7ed58d40cf8a113fdcc0b926ed57b3ec84ce3bdea5d76b9eab25490a70103fbefb8347915a1c61522e20e1ad5f0b51f63a94a305eba7a447f1e11f2f02
• Download URL:
  https://stacks.cdc.gov/view/cdc/187175/cdc_187175_DS1.pdf
• File Type:
  [PDF - 1.58 MB ]