Effect of metoprolol in a chronic murine model of cardiotoxicity induced by doxorubicin and trastuzumab

Introduction Trastuzumab (anti ErbB2 targeted therapy) and anthracyclin can lead to a synergistic cardiotoxicity with a severe decrease of cardiac function. To date, a cardioprotective treatment is not recommended in all patients. Objective Our objective was to define whether metoprolol (β1blocker) used as a cardioprotective treatment was efficient to prevent signs of chronic cardiotoxicity induced by doxorubicin and trastuzumab. Method Males C57Bl/6 mice ( n  = 60) were injected during 2 weeks with intraperitoneal (IP) doxorubicin (total dose: 24 mg/kg) or saline, and then with IP trastuzumab (total dose of 10 mg/kg) or saline for 2 more weeks. Half of mice received metoprolol (100 mg/kg) in drinking water 10 days before starting protocol and during all the study (42 days). A functional exploration was carried out by transthoracic echocardiography. Biological analysis included quantification of plasma troponin I, cardiac transcript using RT-qPCR, signaling pathways using Western Blotting and immunohistology. Results We observed an excess of mortality in the metroprolol group (22% vs. 7% P Conclusion Albeit previous work suggested a cross-regulation between ErbB2 and β adrenergic signaling pathway, our data indicated that metoprolol used as cardioprotective treatment, did not protect heart from toxicity induced by doxorubicin and trastuzumab.