Rationale: In the breast cancer setting, anti-cancer therapies, including Doxorubicin (DOX) and Trastuzumab (TRZ), are associated with an increased risk of cardiotoxicity. There is a need to develop prophylactic cardioprotective agents to mitigate the cardiotoxic side effects of these common anti-cancer drugs.
Objective: To investigate whether the anti-oxidant, N-acetylcysteine amide (NACA), can attenuate the drug-induced heart failure caused by DOX+TRZ in a murine model.
Methods: A total of 100 female mice received one of the following drug regimens: i) saline; ii) NACA; iii) DOX; iv) TRZ; v) DOX+TRZ; vi) NACA+DOX; vii) NACA+TRZ; and viii) NACA+DOX+TRZ. Serial echocardiography was performed over a 10-day study period, after which the mice were euthanized for histological and biochemical analyses.
Results: In mice receiving DOX, left ventricular ejection fraction (LVEF) decreased from 73±4% to 43±2% at day 10. In mice receiving DOX+TRZ, LVEF decreased from 72±3% to 32±2% at day 10. Prophylactic administration of NACA to mice receiving DOX or DOX+TRZ was cardio-protective with an LVEF of 62±3% and 55±3% at day 10, respectively. Histological and biochemical analyses demonstrated loss of cellular integrity, increased oxidative stress (OS), and increased cardiac apoptosis in mice treated with DOX+TRZ which was attenuated by the prophylactic administration of NACA.
Conclusion: NACA attenuates the cardiotoxic side effects of DOX+TRZ in a murine model of chemotherapy induced cardiac dysfunction by decreasing OS and apoptosis. / October 2015
| Identifer | oai:union.ndltd.org:MANITOBA/oai:mspace.lib.umanitoba.ca:1993/30722 |
| Date | 04 September 2015 |
| Creators | Goyal, Vineet |
| Contributors | Jassal, Davinder (Physiology and Pathophysiology) Singal, Pawan (Physiology and Pathophysiology), Ravandi, Amir ( Physiology and Pathophysiology) Kardami, Elissavet (Physiology and Pathophysiology) Wigle, Jeff (Biochemistry & Medical Genetics) |
| Source Sets | University of Manitoba Canada |
| Detected Language | English |
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