The Effects of Fisetin on the Respiratory Activity of Isolated Mitochondria

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 precise mechanisms by which flavonoids exert their beneficial or toxic actions remain unclear. The present work was planned to investigate the action of fisetin on respiratory activity of isolated rat liver mitochondria. Male Wistar rats, weighing 200 to 280 g, fed with a standard laboratory diet were utilized. Oxidative phosphorylation and energy transduction were evaluated in isolated mitochondria. Mitochondrial respiration was measured polarographically. In isolated mitochondria, fisetin diminished state III respiration dependent on succinate or α-ketoglutarate, increased state IV respiration with the FAD-dependent substrate and diminished the respiratory control and ADP/O ratios. A reduction in the cellular ATP levels and an inhibitory action on energy-dependent processes are expected responses to a decrease in the efficiency of mitochondrial energy transduction. The data of the present work show that fisetin is able to affect mitochondrial energy metabolism.