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. 2021 Oct 7;171(5):601–605. doi: 10.1007/s10517-021-05277-2

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

N V Belosludtseva 1, V S Starinets 1, K N Belosludtsev 1,✉
PMCID: PMC8494602  PMID: 34617185

Abstract

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 3UDNP. 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 Ca2+-dependent mitochondrial permeability transition pore. In a concentration of 10 μM, dapagliflozin significantly decreases the rate of H2O2 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.

Key Words: dapagliflozin, mitochondria, mitochondrial permeability transition pore, mitochondrial respiration, reactive oxygen species

Footnotes

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 171, No. 5, pp. 572-576, May, 2021

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