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Emerging Cardioprotective Strategies Beyond Dexrazoxane: SGLT2 Inhibitors, Drug Repurposing, and Mitochondrial

Bahareh Basirpour1,2, Hamidreza Mohammadi3, Nasibeh Hemati1,3

  • 1Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.

Journal of Applied Toxicology : JAT
|June 22, 2026
PubMed

Insights

New cardioprotective strategies beyond dexrazoxane are emerging to combat doxorubicin (DOX)-induced cardiotoxicity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors show promise for preserving heart function during cancer therapy.

Area of Science:

  • Cardiology
  • Oncology
  • Pharmacology

Background:

  • Doxorubicin (DOX) is a vital chemotherapy agent but causes significant cardiotoxicity, limiting its use.
  • Current cardioprotective options like dexrazoxane have limitations, necessitating novel approaches.
  • DOX-induced cardiotoxicity involves complex mechanisms including mitochondrial dysfunction and metabolic dysregulation.

Purpose of the Study:

  • To review emerging cardioprotective strategies against DOX-induced cardiotoxicity.
  • To evaluate novel approaches including SGLT2 inhibitors, drug repurposing, and mitochondrial-targeted therapies.
  • To compare these strategies based on mechanistic insights and clinical development status.

Main Methods:

  • Systematic review of current literature on DOX cardiotoxicity and cardioprotective agents.
  • Analysis of mechanistic data and translational evidence for emerging therapies.
  • Comparative assessment of SGLT2 inhibitors, repurposed drugs, and mitochondrial interventions.

Main Results:

  • SGLT2 inhibitors represent a clinically advanced and mechanistically integrated cardioprotective strategy.
  • Repurposed drugs and mitochondrial-targeted treatments offer complementary but variable cardioprotective potential.
  • DOX cardiotoxicity is a multi-systemic disorder requiring comprehensive therapeutic interventions.

Conclusions:

  • SGLT2 inhibitors are a leading candidate for cardioprotection against anthracycline-induced cardiotoxicity.
  • Combination therapies and personalized cardioprotection strategies are crucial for future cardiac preservation.
  • Further research is needed to optimize novel cardioprotective approaches for cancer patients.
Keywords:
DOX cardiotoxicitySGLT2 inhibitorscardio‐oncologydexrazoxaneexactness cardioprotectionferroptosismitochondrial brokennessmitochondrial elementsmitophagysedate repurposing

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