Faculty Collaboration Database

Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs. Am J Physiol Lung Cell Mol Physiol 2005 Nov;289(5):L788-97

Date

07/05/2005

Pubmed ID

15994278

DOI

10.1152/ajplung.00064.2005

Scopus ID

2-s2.0-27144481919 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by approximately 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.

Author List

Audi SH, Bongard RD, Krenz GS, Rickaby DA, Haworth ST, Eisenhauer J, Roerig DL, Merker MP

Author

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Benzoquinones
Chronic Disease
Hyperoxia
In Vitro Techniques
Kinetics
Lung
NAD(P)H Dehydrogenase (Quinone)
Oxidation-Reduction
Perfusion
Pulmonary Circulation
Rats
Rats, Sprague-Dawley