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Duroquinone reduction during passage through the pulmonary circulation.
Said H Audi1, Robert D Bongard, Christopher A Dawson
1Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin 53201, USA. audis@marquette.edu
Summary
The lungs reduce duroquinone (DQ) to its stable hydroquinone form, influencing plasma redox status. Lung NAD(P)H-quinone oxidoreductase 1 (NQO1) is key in this pulmonary disposition.
Area of Science:
- Pulmonary physiology and biochemistry
- Redox homeostasis and xenobiotic metabolism
Background:
- The lungs significantly impact the redox state of circulating compounds.
- Understanding pulmonary disposition of redox-active molecules is crucial for assessing their physiological effects.
Purpose of the Study:
- To investigate the kinetics and mechanisms of pulmonary disposition for redox-active compounds.
- To characterize the lung's role in the metabolism of amphipathic quinones using duroquinone (DQ) as a model.
Main Methods:
- Experiments conducted on isolated rat and mouse lungs.
- Measurement of duroquinone (DQ) and durohydroquinone (DQH2) concentrations in lung venous effluent.
- Infusion and injection of DQ or DQH2 into the pulmonary artery to assess lung processing.
Main Results:
- Maximum net rates of DQ reduction to DQH2 were approximately 4.9 (rat) and 2.5 (mouse) µmol·min⁻¹·g dry lung wt⁻¹.
- DQ reduction is primarily dicumarol-sensitive, implicating NAD(P)H-quinone oxidoreductase 1 (NQO1).
- DQH2 reoxidation is cyanide-sensitive, suggesting involvement of mitochondrial complex III.
Conclusions:
- Lung NQO1 plays a dominant role in reducing DQ to DQH2.
- The lungs convert redox-cycling quinones into stable hydroquinones, impacting circulating redox status.
- Pulmonary disposition mechanisms are critical for managing redox-active compounds in circulation.