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Citation
Tags
HERO ID
1493906
Reference Type
Journal Article
Subtype
Abstract
Title
Importance of microsomal epoxide hydrolase (mEH) in toxicity, metabolism and formation of covalent protein adducts from the volatile air pollutant, naphthalene (NA): Comparison of mEH null and wild type (WT) mice
Author(s)
Krawiec, DM; Sutherland, K; Morin, D; Thornton, J; Buckpitt, A; Van Winkle, L
Year
2008
Is Peer Reviewed?
Yes
Journal
FASEB Journal
ISSN:
0892-6638
EISSN:
1530-6860
Volume
22
Language
English
Web of Science Id
WOS:000208467804301
URL
http://
://WOS:000208467804301
Exit
Abstract
Human exposure to NA is due to combustion of both environmental and man-made materials. Toxicity of NA is P450-dependent, occurring in murine, but not rat, airways. However, the extent to which specific metabolic pathways (to epoxides, quinones and diol epoxides) contribute to cytotoxicity and the formation of covalent protein adducts is unknown. Upon inhalation exposure to NA (4h at 5–20 ppm) male mEH null animals had increased cytotoxicity in the bronchioles, but decreased susceptibility in the trachea and lobar bronchus as compared to WT mice, despite having a normal pattern of P450-containing CC10 positive Clara cells. Formation rates of NA metabolites (conjugates plus diol) in the trachea were lower in EH null animals, but equivalent in the airways compared to WT. As expected, rates of diol formation were undetected/low in mEH null animals. Protein adducts detected after ip administration of NA were 2–4 fold higher in airway epithelium than elsewhere in the lung, and EH null animals showed significantly higher levels compared to WT. Bound liver adducts showed no differences between mEH and WT animals. These studies suggest that metabolites (1,2-quinone, diol epoxide) arising via the diol pathway are not critical to NA toxicity or formation of covalent adducts in distal airway epithelium. This work also suggests that there are compensatory changes associated with disruption of mEH.
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Naphthalene
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Naphthalene (2021 Evidence mapping publication)
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