Modulatory effect of metformin on cardiotoxicity induced by doxorubicin via the MAPK and AMPK pathways

Area of Science:

• Cardiology
• Pharmacology
• Molecular Biology

Background:

• Doxorubicin (DOX) is a potent anticancer drug with dose-limiting cardiotoxicity.
• Metformin (Met), a common antidiabetic medication, has demonstrated potential cardioprotective properties.
• The interaction between DOX cardiotoxicity and Met's effects requires further investigation.

Purpose of the Study:

• To investigate the potential of Metformin to attenuate Doxorubicin-induced cardiotoxicity.
• To elucidate the underlying mechanisms of Metformin's protective effects against DOX-induced cardiac damage.

Main Methods:

• DOX-induced cardiotoxicity models were established in vitro using H9C2 cells and in vivo using Sprague-Dawley rats.
• Cell viability, apoptosis markers (caspase-3, Bax, Bcl-2), oxidative stress markers, and cardiac function were assessed.
• Key signaling pathways, including AMPK and MAPK, were analyzed.

Main Results:

• Metformin inhibited DOX-induced H9C2 cell growth inhibition and apoptosis.
• In vivo, Metformin improved cardiac function, reduced serum cardiac injury markers, and ameliorated cardiac pathology.
• Metformin suppressed DOX-induced increases in cleaved caspase-3 and Bax, prevented Bcl-2 downregulation, activated AMPK, and inhibited MAPK signaling.

Conclusions:

• Metformin exhibits significant protective effects against Doxorubicin-induced cardiotoxicity.
• These protective effects are mediated by the reduction of oxidative stress and apoptosis.
• Metformin's action involves the regulation of AMPK and MAPK signaling pathways.