action of quercetin on the mitochondrial NADH to NAD+ ratio in the isolated perfused rat liver

Abstract It has been suggested that active forms of quercetin (O-semiquinones) are able to oxidize NADH in mammalian cells. The purpose of this study was to investigate this proposition by measuring the β-hydroxybutyrate to acetoacetate ratio as an indicator of the mitochondrial NADH/NAD + redox ratio in the isolated perfused rat liver. The NADH to NAD + ratio was reduced by quercetin; half-maximal reduction occurred at a concentration of 32.6 μM. Additionally, quercetin (25 to 300 μM) stimulated the Krebs cycle ( 14 CO 2 production) and inhibited oxygen uptake (50 to 300 μM). Low quercetin concentrations (25 μM) stimulated oxygen uptake. The results of the present work confirm the hypothesis that quercetin is able to participate in the oxidation of NADH in mammalian cells, shifting the cellular conditions to a more oxidized state (prooxidant activity). Stimulation of the Krebs cycle was probably caused by the increased NAD + availability whereas the decreased NADH availability and the inhibition of mitochondrial energy transduction could be the main causes for oxygen uptake inhibition.