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Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of

Kun-Ling Tsai1,2, Pei-Ling Hsieh3, Wan-Ching Chou1

  • 1Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Cell & Bioscience
|February 27, 2021
PubMed
Abstract

Insights

Dapagliflozin (DAPA) protects against cardiac ischemia/reperfusion injury by reducing oxidative stress and apoptosis. This sodium-glucose cotransporter 2 inhibitor modulates the AMPK/PKC/NADPH oxidase pathway, improving cardiac function.

Area of Science:

  • Cardiovascular Science
  • Molecular Biology
  • Pharmacology

Background:

  • Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, shows promise in preventing cardiovascular events.
  • The precise mechanisms behind DAPA's cardioprotective effects, particularly in ischemia/reperfusion (I/R) injury, are not fully understood.

Purpose of the Study:

  • To investigate the cardioprotective effects of DAPA against cardiac ischemia/reperfusion (I/R) injury.
  • To elucidate the underlying molecular mechanisms, focusing on the AMPK/PKC/NADPH oxidase pathway.

Main Methods:

  • In vitro experiments using cardiac myoblast H9c2 cells under hypoxia/reoxygenation (H/R).
  • In vivo studies using rat models of cardiac I/R injury.
  • Assessment of molecular signaling pathways, oxidative stress markers, mitochondrial function, apoptosis, and cardiac dysfunction via echocardiography.

Main Results:

  • DAPA treatment induced AMPK phosphorylation and downregulated PKC in H9c2 cells under H/R.
  • DAPA diminished H/R-induced oxidative stress and protected mitochondrial function via the AMPK/PKC/NADPH oxidase pathway.
  • DAPA reversed H/R-induced apoptosis, improved I/R-induced cardiac dysfunction in rats, and reduced myocardial infarction markers.

Conclusions:

  • DAPA treatment ameliorates cardiac I/R injury by reducing oxidative stress and apoptosis.
  • Modulation of the AMPK pathway is a key mechanism by which DAPA exerts its cardioprotective effects.
  • DAPA demonstrates potential as a therapeutic agent for mitigating cardiac dysfunction following I/R events.
Keywords:
AMPKDapagliflozinIschemia/reperfusion injury

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