title: Duroquinone reduction during passage through the pulmonary circulation.
abstract: The lungs can substantially influence the redox status of redox-active plasma constituents. Our objective was to examine aspects of the kinetics and mechanisms that determine pulmonary disposition of redox-active compounds during passage through the pulmonary circulation. Experiments were carried out on rat and mouse lungs with 2,3,5,6-tetramethyl-1,4-benzoquinone [duroquinone (DQ)] as a model amphipathic quinone reductase substrate. We measured DQ and durohydroquinone (DQH2) concentrations in the lung venous effluent after injecting, or while infusing, DQ or DQH2 into the pulmonary arterial inflow. The maximum net rates of DQ reduction to DQH2 in the rat and mouse lungs were approximately 4.9 and 2.5 micromol. min(-1).g dry lung wt(-1), respectively. The net rate was apparently the result of freely permeating access of DQ and DQH2 to tissue sites of redox reactions, dominated by dicumarol-sensitive DQ reduction to DQH2 and cyanide-sensitive DQH2 reoxidation back to DQ. The dicumarol sensitivity along with immunodetectable expression of NAD(P)H-quinone oxidoreductase 1 (NQO1) in the rat lung tissue suggest cytoplasmic NQO1 as the dominant site of DQ reduction. The effect of cyanide on DQH2 oxidation suggests that the dominant site of oxidation is complex III of the mitochondrial electron transport chain. If one envisions DQ as a model compound for examining the disposition of amphipathic NQO1 substrates in the lungs, the results are consistent with a role for lung NQO1 in determining the redox status of such compounds in the circulation. For DQ, the effect is conversion of a redox-cycling, oxygen-activating quinone into a stable hydroquinone.
authors.affiliation: Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin 53201, USA. audis@marquette.edu
authors.forename: Said H
authors.initials: SH
authors.lastname: Audi
authors.forename: Robert D
authors.initials: RD
authors.lastname: Bongard
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Dawson
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.forename: David L
authors.initials: DL
authors.lastname: Roerig
authors.forename: Marilyn P
authors.initials: MP
authors.lastname: Merker
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D006873:Hydroquinones / Q000493:pharmacokinetics; D007269:Injections, Intra-Arterial; D007700:Kinetics; D008168:Lung / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010084:Oxidation-Reduction; D011651:Pulmonary Artery / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D014018:Tissue Distribution
chemical_list: D016227:Benzoquinones; D006873:Hydroquinones; C016421:duroquinol; C034257:duroquinone