Abstract
Flavonols, which possess the Bโcatechol ring, as quercetin, are capable of producing oโhemiโ quinones and to oxidize NADH in a variety of mammalian cells. The purpose of this study was to investigate whether fisetin affects the liver energy metabolism and the mitochondrial NADH to NAD^+^ ratio. The action of fisetin on hepatic energy metabolism was investigated in the perfused rat liver and isolated mitochondria. In isolated mitochondria, fisetin decreased the respiratory control and ADP/O ratios with the substrates ฮฑโketoglutarate and succinate. In the presence of ADP, respiration of isolated mitochondria was inhibited with both substrates, indicating an inhibitory action on the ATPโsynthase. The stimulation of the ATPase activity of coupled mitochondria and the inhibition of NADHโoxidase activity pointed toward a possible uncoupling action and the interference of fisetin with mitochondrial energy transduction mechanisms. In livers from fasted rats, fisetin inhibited ketogenesis from endogenous sources. The ฮฒโhydroxybutyrate/ acetoacetate ratio, which reflects the mitochondrial NADH/NAD^+^ redox ratio, was also decreased. In addition, fisetin (200 ฮผM) increased the production of ^14^CO~2~ from exogenous oleate. The results of this investigation suggest that fisetin causes a shift in the mitochondrial redox potential toward a more oxidized state with a clear predominance of its prooxidant activity. ยฉ 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:117โ126, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20367