Mitigating ibrutinib-induced ventricular arrhythmia and cardiac dysfunction with metformin
Pengsha Li1, Daiqi Liu1, Pan Gao1
1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University Tianjin China.
Cancer Innovation
|November 15, 2024
Summary
Metformin protects against ibrutinib-induced cardiotoxicity in mice by improving cardiac function and reducing arrhythmia. This study highlights metformin
Area of Science:
- Cardiovascular toxicology
- Pharmacology
- Oncology
Background:
- Ibrutinib, a Bruton's tyrosine kinase inhibitor, treats B cell cancers but causes cardiotoxicity.
- Investigating ibrutinib-induced cardiotoxicity mechanisms and metformin's protective effects is crucial for patient safety.
Purpose of the Study:
- To elucidate the mechanism of ibrutinib-induced cardiotoxicity.
- To evaluate metformin's efficacy in preventing and reversing ibrutinib-induced cardiac damage.
Main Methods:
- Male C57BL/6J mice received ibrutinib (30 mg/kg/day) to induce cardiotoxicity.
- Metformin (200 mg/kg/day) was administered starting one week before ibrutinib.
- Cardiac function, electrophysiology, and molecular pathways (PI3K-AKT, AMPK, apoptosis) were assessed.
Main Results:
- Ibrutinib induced ventricular arrhythmia, conduction abnormalities, and reduced ejection fraction.
- Metformin pretreatment reversed these cardiotoxic effects.
- Ibrutinib decreased PI3K-AKT activity, leading to cardiomyocyte apoptosis; metformin upregulated AMPK and PI3K-AKT.
Conclusions:
- Metformin effectively mitigates ibrutinib-induced cardiotoxicity and cardiac dysfunction.
- Metformin enhances AMPK and PI3K-AKT pathway activity, protecting cardiomyocytes.
- Metformin shows potential for improving cardiovascular safety in patients treated with ibrutinib.
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