The cardioprotective role of NACA in the prevention of Doxorubicin and Trastuzumab mediated cardiac dysfunction
dc.contributor.author | Goyal, Vineet | |
dc.contributor.examiningcommittee | Ravandi, Amir ( Physiology and Pathophysiology) Kardami, Elissavet (Physiology and Pathophysiology) Wigle, Jeff (Biochemistry & Medical Genetics) | en_US |
dc.contributor.supervisor | Jassal, Davinder (Physiology and Pathophysiology) Singal, Pawan (Physiology and Pathophysiology) | en_US |
dc.date.accessioned | 2015-09-04T13:37:34Z | |
dc.date.available | 2015-09-04T13:37:34Z | |
dc.date.issued | 2015 | |
dc.degree.discipline | Physiology and Pathophysiology | en_US |
dc.degree.level | Master of Science (M.Sc.) | en_US |
dc.description.abstract | 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. | en_US |
dc.description.note | October 2015 | en_US |
dc.identifier.uri | http://hdl.handle.net/1993/30722 | |
dc.language.iso | eng | en_US |
dc.rights | open access | en_US |
dc.subject | Cardio-Oncology | en_US |
dc.subject | Heart Failure | en_US |
dc.subject | Cardiotoxicity | en_US |
dc.subject | Doxorubicin | en_US |
dc.subject | Trastuzumab | en_US |
dc.subject | N-Acetylcysteine Amide | en_US |
dc.subject | Echocardiography | en_US |
dc.subject | Apoptosis | en_US |
dc.title | The cardioprotective role of NACA in the prevention of Doxorubicin and Trastuzumab mediated cardiac dysfunction | en_US |
dc.type | master thesis | en_US |