The Cardioprotective Role of Probucol Against Anthracycline and Trastuzumab-Mediated Cardiotoxicity - 10/08/11
Reprint requests: Davinder S. Jassal, MD, FACC, FRCPC, Assistant Professor of Cardiology, Radiology and Physiology, Section of Cardiology, Department of Internal Medicine, Rm Y3010, Bergen Cardiac Care Centre, St. Boniface General Hospital, 409 Tache Avenue, Winnipeg, Manitoba, Canada, R2H 2A6.Abstract |
Objective |
Although the combination of doxorubicin (Dox) and trastuzumab (Trz) reduces breast cancer progression and recurrence, it is limited by significant cardiotoxic side effects. Little is known about the utility of antioxidants in the prevention of this drug-induced cardiomyopathy. The aim of the study was to determine whether the antioxidant probucol (Prob) would be useful in attenuating Dox and Trz-mediated cardiotoxicity.
Methods |
A total of 114 mice were randomized to treatment with Trz, Dox, or Dox+Trz. Within each arm, mice received prophylactic treatment with placebo or Prob. Serial murine echocardiography with tissue Doppler imaging was performed daily for 10 days. At 10 days posttreatment, the hearts were removed for histopathologic and Western blot analyses.
Results |
Left ventricular cavity dimensions and systolic parameters were preserved in mice prophylactically treated with Prob after the administration of Dox+Trz. Although the combination of Dox+Trz demonstrated >80% mortality at day 5, prophylactic treatment with Prob reduced mortality to 40% at day 10. There was decreased histologic evidence of cardiac damage and reduced apoptosis due to Dox+Trz in mice pretreated with Prob.
Conclusion |
The cardiotoxic effects of Dox+Trz are partially attenuated by the prophylactic administration of the antioxidant Prob.
Le texte complet de cet article est disponible en PDF.Keywords : Cardiomyopathy, Cardioprotection, Doxorubicin, Probucol, Trastuzumab
Abbreviations : Dox, EF, FS, HER2, LV, LVEDD, Prob, SR, TDI, Trz
Plan
| This work was supported by grants from the Canadian Breast Cancer Foundation, St. Boniface General Hospital and Research Foundation, Manitoba Health Research Council, and Health Sciences Centre Research Foundation. J.R.W. is the recipient of a studentship from the Manitoba Health Research Council, the Woman’s Health Research Foundation of Canada, and the Deer Lodge Hospital Staff Association Memorial Fund Award (Manitoba Medical College Foundation). P. K.S. is the holder of the Naranjan S. Dhalla Chair in Cardiovascular Research supported by the St. Boniface Hospital and Research Foundation. D.S.J. is the recipient of the Heart and Stroke Foundation New Investigator award. |
Vol 24 - N° 6
P. 699-705 - juin 2011 Retour au numéro
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