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 beta-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 microM. Additionally, quercetin (25 to 300 microM) stimulated the Krebs cycle ( (14)CO (2) production) and inhibited oxygen uptake (50 to 300 microM). Low quercetin concentrations (25 microM) 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.

The p-coumaric acid, a phenolic acid, occurs in several plant species and, consequently, in many foods and beverages of vegetable origin. Its antioxidant activity is well documented, but there is also a single report about an inhibitory action on the monocarboxylate carrier, which operates in the plasma and mitochondrial membranes. The latter observation suggests that p-coumaric acid could be able to inhibit gluconeogenesis and related parameters. The present investigation was planned to test this hypothesis in the isolated and hemoglobin-free perfused rat liver. Transformation of lactate and alanine into glucose (gluconeogenesis) in the liver was inhibited by p-coumaric acid (IC50 values of 92.5 and 75.6 microM, respectively). Transformation of fructose into glucose was inhibited to a considerably lower degree (maximally 28%). The oxygen uptake increase accompanying gluconeogenesis from lactate was also inhibited. Pyruvate carboxylation in isolated intact mitochondria was inhibited (IC50 = 160.1 microM); no such effect was observed in freeze-thawing disrupted mitochondria. Glucose 6-phosphatase and fructose 1,6-bisphosphatase were not inhibited. In isolated intact mitochondria, p-coumaric acid inhibited respiration dependent on pyruvate oxidation but was ineffective on respiration driven by succinate and beta-hydroxybutyrate. It can be concluded that inhibition of pyruvate transport into the mitochondria is the most prominent primary effect of p-coumaric acid and also the main cause for gluconeogenesis inhibition. The existence of additional actions of p-coumaric acid, such as enzyme inhibitions and interference with regulatory mechanisms, cannot be excluded.

Palavras-chave: Streptococcus pyogenes, faringoamigdalite, infecção estreptocócica.