Details:

Alternative Title:
Xenobiotica
Publisher's site:
http://dx.doi.org/10.1080/00498254.2017.1329569
Personal Author:
Wisnewski, Adam V. ; Kanyo, Jean ; Asher, Jennifer ; Goodrich, James A. ; Barnett, Grace ; ... More +
Wisnewski, Adam V. ; Kanyo, Jean ; Asher, Jennifer ; Goodrich, James A. ; Barnett, Grace ; Patrylak, Lyn ; Liu, Jian ; Redlich, Carrie A. ; Nassar, Ala F. Less -
Description:
1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma. 2. "Self" molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized. 3. This study employed unique approaches to identify and characterize "self" targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O|, or O| plus ∼200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS. 4. The low-molecular weight (<3 kDa) fraction of HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified 783.26 and 476.18 m/z [M+H]| ions with high energy collision-induced dissociation (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin. 5. In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with "self" molecules in the lower airways.
Subject:
[+]
Article
Exposure
Glutathione
Hexamethylene Diisocyanate
Tracheostomy

Source:
Xenobiotica. 48(5):488-497.
Pubmed ID:
28489470
Pubmed Central ID:
PMC5863241
Document Type:
Journal Article
Funding:
R01 OH010941/OH/NIOSH CDC HHS/United States
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:aa58c3e7f08a5aeaf29dc49bde5bb36611b09d16a74dd7d8974cde8ca64824e6
File Type:

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