This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Naphthalene (NA) and 1-nitronaphthalene (1-NN) are ambient air pollutants which undergo bioactivation by pulmonary cytochrome P450 monooxygenases and deplete Glutathione. Reactive metabolites become bound covalently to cellular proteins and this process has been implicated in cellular injury associated with these agents in rodent models. The relevance of rodent models in assessing the importance of chemicals which require bioactivation is not clear because of the 10 to 100 fold lower activities of cytochrome P450 monooxygenases in primates compared to rodent lungs. Besides being a target for bioactivated toxicants, the airway is also one of the most susceptible sites for acute inflammatory response. Inflammation results in a strong suppression of cytochrome P450 dependent metabolism at least in extrahepatic tissues. Recent work has established and validated a primate model for human asthma which involves exposure to house dust mite antigen (HDMA) and ozone (O3). Accordingly these studies were designed to measure the formation of, and identity of reactive metabolite protein adducts in rhesus macaques and to determine whether treatments which produce an asthmatic response alter the rates and or nature of protein adducts generated.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-50
Application #
8357246
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$75,629
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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Carroll, Timothy D; Jegaskanda, Sinthujan; Matzinger, Shannon R et al. (2018) A Lipid/DNA Adjuvant-Inactivated Influenza Virus Vaccine Protects Rhesus Macaques From Uncontrolled Virus Replication After Heterosubtypic Influenza A Virus Challenge. J Infect Dis 218:856-867
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