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dc.contributor.supervisor Jassal, Davinder (Physiology and Pathophysiology) Singal, Pawan (Physiology and Pathophysiology) en_US
dc.contributor.author Goyal, Vineet
dc.date.accessioned 2015-09-04T13:37:34Z
dc.date.available 2015-09-04T13:37:34Z
dc.date.issued 2015
dc.identifier.uri http://hdl.handle.net/1993/30722
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.rights info:eu-repo/semantics/openAccess
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 info:eu-repo/semantics/masterThesis
dc.degree.discipline Physiology and Pathophysiology en_US
dc.contributor.examiningcommittee Ravandi, Amir ( Physiology and Pathophysiology) Kardami, Elissavet (Physiology and Pathophysiology) Wigle, Jeff (Biochemistry & Medical Genetics) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note October 2015 en_US


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