Effect of Dapagliflozin on the Functioning of Rat Liver Mitochondria In Vitro

We studied the effect of a new hypoglycemic compound dapagliflozin on the functioning of rat liver mitochondria. Dapagliflozin in concentrations of 10-20 μM had no effect on the parameters of respiration and oxidative phosphorylation of rat liver mitochondria. Increasing dapagliflozin concentration to 50 μM led to a significant inhibition of mitochondrial respiration in states 3 and 3U(DNP). Dapagliflozin in this concentration significantly reduced calcium retention capacity of rat liver mitochondria. These findings indicate a decline in the resistance of rat liver mitochondria to induction of Ca(2+)-dependent mitochondrial permeability transition pore. In a concentration of 10 μM, dapagliflozin significantly decreases the rate of H(2)O(2) formation in rat liver mitochondria, which attested to an antioxidant effect of this compound. Possible mitochondrion-related mechanisms of the protective action of dapagliflozin on liver cells are discussed.