THE EFFECTS OF FISETIN ON NADH OXIDASE, SUCCINATE OXIDASE, ATPase ACTIVITIES AND TMPD/ASCORBATE OXIDATION

Abstract

Fisetin (3,7,3´,4´-tetrahydroxyflavone) is a flavonoid dietary ingredient found in fruits and vegetables. It exhibits a wide variety of pharmacological properties, including neurotrophic, antioxidant, antiinflammatory, antidiabetic, antioangiogenic and anticarcinogenic effects. The most known biological effect of flavonoids is their antioxidant action. At high doses, however, the potentially toxic effects of fisetin and other flavonoids have to be taken into account, because it has been shown that in elevated doses, flavonoids, can act as mutagens, prooxidants with the generation of free radicals and as inhibitors of enzymes involved in energy and hormonal metabolism. The present work was planned to investigate the action of fisetin on specific points in the electron transport chain and ATPase activity of rat liver mitochondria. Male Wistar rats, weighing 200 to 280 g, fed with a standard laboratory diet were utilized. The ATPase activity of coupled mitochondria was increased in a dose-dependent manner; maximal stimulation of 134% was achieved at the concentration of 400 µM. When disrupted or uncoupled mitochondria were used as the enzyme source, the ATPase activity was inhibited by 43.6% and 36.7%, respectively, by fisetin 300 µM. The NADH oxidase activity was inhibited, but fisetin did not change the succinate oxidase activity and the TMPD/ascorbate oxidation. Fisetin affects electron flow as indicated by the inhibition of NADH oxidation in disrupted mitochondria probably by acting on the respiratory chain complex I, which is in accordance with previous study. Its effects on the ATPase activity suggest that fisetin is also an uncoupler of oxidative phosphorylation.