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Coenzyme Q₁ redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia

Departments of ¹Biomedical Engineering, ²Mathematics, Statistics and Computer Science, Marquette University; Departments of ³Pulmonary and Critical Care Medicine, ⁴Anesthesiology, and ⁵Pharmacology/Toxicology, Medical College of Wisconsin; and ⁶Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin

Submitted 14 February 2008 ; accepted in final form 14 August 2008

The objective was to evaluate the pulmonary disposition of the ubiquinone homolog coenzyme Q₁ (CoQ₁) on passage through lungs of normoxic (exposed to room air) and hyperoxic (exposed to 85% O₂ for 48 h) rats. CoQ₁ or its hydroquinone (CoQ₁H₂) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ₁H₂ and CoQ₁ were measured. CoQ₁H₂ appeared in the venous effluent when CoQ₁ was infused, and CoQ₁ appeared when CoQ₁H₂ was infused. In normoxic lungs, CoQ₁H₂ efflux rates when CoQ₁ was infused decreased by 58 and 33% in the presence of rotenone (mitochondrial complex I inhibitor) and dicumarol [NAD(P)H-quinone oxidoreductase 1 (NQO1) inhibitor], respectively. Inhibitor studies also revealed that lung CoQ₁H₂ oxidation was via mitochondrial complex III. In hyperoxic lungs, CoQ₁H₂ efflux rates when CoQ₁ was infused decreased by 23% compared with normoxic lungs. Based on inhibitor effects and a kinetic model, the effect of hyperoxia could be attributed predominantly to 47% decrease in the capacity of complex I-mediated CoQ₁ reduction, with no change in the other redox processes. Complex I activity in lung homogenates was also lower for hyperoxic than for normoxic lungs. These studies reveal that lung complexes I and III and NQO1 play a dominant role in determining the vascular concentration and redox status of CoQ₁ during passage through the pulmonary circulation, and that exposure to hyperoxia decreases the overall capacity of the lung to reduce CoQ₁ to CoQ₁H₂ due to a depression in complex I activity.

mathematical modeling; NADH: ubiquinone oxidoreductase; NAD(P)H: quinone oxidoreductase 1; ubiquinol-cytochrome-c oxidoreductase