The cardioprotective role of NACA in the prevention of Doxorubicin and Trastuzumab mediated cardiac dysfunction

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dc.contributor.authorGoyal, Vineet
dc.contributor.examiningcommitteeRavandi, Amir ( Physiology and Pathophysiology) Kardami, Elissavet (Physiology and Pathophysiology) Wigle, Jeff (Biochemistry & Medical Genetics)en_US
dc.contributor.supervisorJassal, Davinder (Physiology and Pathophysiology) Singal, Pawan (Physiology and Pathophysiology)en_US
dc.date.accessioned2015-09-04T13:37:34Z
dc.date.available2015-09-04T13:37:34Z
dc.date.issued2015
dc.degree.disciplinePhysiology and Pathophysiologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractRationale: 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.noteOctober 2015en_US
dc.identifier.urihttp://hdl.handle.net/1993/30722
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectCardio-Oncologyen_US
dc.subjectHeart Failureen_US
dc.subjectCardiotoxicityen_US
dc.subjectDoxorubicinen_US
dc.subjectTrastuzumaben_US
dc.subjectN-Acetylcysteine Amideen_US
dc.subjectEchocardiographyen_US
dc.subjectApoptosisen_US
dc.titleThe cardioprotective role of NACA in the prevention of Doxorubicin and Trastuzumab mediated cardiac dysfunctionen_US
dc.typemaster thesisen_US
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