Phloretin ameliorates arsenic trioxide induced mitochondrial dysfunction in H9c2 cardiomyoblasts mediated via...

Area of Science:

• Cardiology
• Mitochondrial Biology
• Pharmacology

Background:

• Arsenic trioxide (ATO) is effective for acute promyelocytic leukemia but causes cardiotoxicity.
• Mitochondrial dysfunction is a key factor in ATO-induced cardiotoxicity.
• Research on ATO's specific effects on mitochondrial function is limited.

Purpose of the Study:

• To investigate the impact of ATO on mitochondrial components and functions.
• To assess ATO's effects on oxidative stress, ATP production, and apoptosis in cardiac cells.
• To evaluate the cardioprotective efficacy of phloretin against ATO toxicity.

Main Methods:

• H9c2 cells were exposed to ATO (5µM).
• Mitochondrial functions, oxidative stress markers, calcium homeostasis, and apoptosis were analyzed.
• The effects of phloretin (2.5 and 5µM) on ATO-treated cells were assessed.

Main Results:

• ATO exposure increased oxidative stress, reduced antioxidant status, impaired mitochondrial function, and induced apoptosis.
• ATO altered intracellular calcium levels and affected key enzymes and transcription factors (Nrf2, xanthine oxidase, aconitase, caspase 3).
• Phloretin demonstrated significant protection against ATO-induced cardiotoxicity by preserving mitochondrial integrity.

Conclusions:

• ATO induces cardiotoxicity through mitochondrial damage and oxidative stress.
• Phloretin exhibits cardioprotective effects by mitigating ATO-induced mitochondrial dysfunction.
• Phloretin holds promise as a cardioprotective agent for cancer patients undergoing ATO chemotherapy.