P470 BERBERINE ASSOCIATED TO DAPAGLIFLOZIN EXERTS SYNERGISTIC CARDIOPROTECTIVE EFFECTS IN CARDIAC CELLS EXPOSED TO THE HER2–BLOKING AGENT TRASTUZUMAB THROUGH PAMPK ACTIVATION AND REDUCTION IN INTERLEUKIN–6 LEVELS

Autor: V Quagliariello, M Scherillo, F Maurea, M Iovine, A Paccone, N Maurea
Rok vydání: 2023
Předmět:
Zdroj: European Heart Journal Supplements. 25:D227-D227
ISSN: 1554-2815
1520-765X
DOI: 10.1093/eurheartjsupp/suad111.532
Popis: Background Trastuzumab has improved the prognosis in patients with HER2–positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio–renal benefits. In the DAPA–HF (Dapagliflozin And Prevention of Adverse–outcomes in Heart Failure) trial, the sodium–glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine is a nutraceutical compound characterized by multiple metabolic effects in patients with/without cardiovascular diseases. Purpose: To investigate on the potential cardioprotective properties of Berberine associated to SGLT2i Dapagliflozin against HER–2 blocking agent–induced cardiotoxicity Methods Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co–incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3 inflammasome, methylglyoxal and leukotrienes–B4. Expression of pAMPK was analyzed through western blot. Moreover, quantification of IL–6 was performed through ELISA method. Results Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p Conclusion Berberine and Dapagliflozin exerts significant cardioprotective effects in cardiac cells exposed to the HER2–bloking agent Trastuzumab. Berberine and Dapagliflozin in combination induces an anti–inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis.
Databáze: OpenAIRE
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