Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Nano-cerium dioxide exposure and arteriolar dysfunction: what is the mechanism?

Authors
Minarchick-VC; Stapleton-PG; Fix-NR; Leonard-SS; Sabolsky-EM; Nurkiewicz-TR
Source
Toxicologist 2014 Mar; 138(1):127
NIOSHTIC No.
20043887
Abstract
Applications of nano-cerium dioxide (CeO2) are potentially endless, but its biologic interactions must first be understood. We have reported that pulmonary CeO2 exposure results in endothelium-dependent and -independent arteriolar dysfunction. Based on these observations, we predict that this dysfunction is mechanistically linked to impaired nitric oxide (NO) signaling. Rats were intratracheally instilled (65 mg) or intravenously injected (IV,100 mg) with CeO2 suspended in saline (5% serum). Mesenteric arterioles were examined post 24 hrs via intravital microscopy or isolated vessels. Arteriolar reactivity was evaluated by using acetylcholine (ACh, 10-9-10-4 M), and spermine NONOate (10-9-10-4 M). The role of NO synthase and cyclooxygenase reactivity was tested in the presence of Ný-Nitro-L-arginine methyl ester hydrochloride (L-NMMA) and/or indomethacin (INDO) (respectively). Soluble guanyl cyclase activator (YC-1) and cyclic guanosine monophosphate mimetic (8-Bromo-cGMP) assessed smooth muscle activation. Electron spin resonance and a free radical analyzer assessed the ability of NO to react with CeO2 and the level of tissue free radicals. At the time of writing, results were similar in both models and exposure routes. Control animals responded normally to increasing concentrations of ACh (80+/-4%) and this dilation was impaired in the presence of L-NMMA (34+/-9%) or INDO (45+/-11%). Pulmonary CeO2 exposure significantly impaired this dilation (30+/-4%). INDO treatment did not alter this impairment (44+/-10%) but there was a partial restoration in function during L-NMMA treatment (51+/-11%). Smooth muscle activation was intact following both exposure routes. CeO2 is capable of reacting with NO and there appears to be minimal changes in free radicals. These results are consistent with the notion that CeO2 exposure impairs endothelial function at least in part via a NO dependent mechanism.
Keywords
Toxicology; Cell-function; Cellular-function; Toxic-effects; Laboratory-animals; Animals; Cell-damage; Nanotechnology; Lung; Exposure-levels; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Muscle-tissue; Models
CAS No.
10102-43-9
Publication Date
20140301
Document Type
Abstract
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
M032014
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona
State
WV
TOP