THE EFFECTS OF FISETIN ON KETOGENESIS AND CITRIC ACID CYCLE IN THE RAT LIVER

Abstract

The most known biological effects of the flavonoids, including quercetin and fisetin, is no doubt their antioxidant action, which represents protection of tissues against the action of free-radicals and diminution of lipid peroxidation. However, the antioxidant and anticancer effects of quercetin and other flavonoids are not an unanimity, since it has been shown that significant protective effects due to quercetin would only be achieved upon the ingestion of high doses. At high doses, however, the potentially toxic effects of quercetin and other flavonoids have to be taken into account. The present work was planned to investigate the effects of fisetin on ketogenesis and citric acid cycle in the rat liver. Male Wistar rats, weighing 200 to 280 g, fed with a standard laboratory diet were utilized. But in this case, livers from 24 h fasted rats were used in all experiments. The isolated liver was perfused in the non-recirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of O2 and CO2 (95:5) by means of a membrane oxygenator and simultaneously heated to 37oC. Ketogenesis (β-hydroxybutyrate and acetoacetoacetate production) from endogenous sources was inhibited by fisetin in the whole concentration range (50-200 µM). The β-hydroxybutyrate to acetoacetoacetate ratio was also reduced, and 14CO2 production from exogenous [1-14C]-oleate was increased by fisetin. 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.