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Defense Date
2006
DOI
https://doi.org/10.25772/6NF6-8H36
Document Type
Thesis
Degree Name
Master of Science
Department
Physiology
First Advisor
Dr. Mohammed Y. Kalimi
Abstract
The antineoplastic drug doxorubicin is widely used in the treatment of various types of cancers including breast, colon and lung cancer. However, doxorubicin has adverse effects on the heart and prolonged doxorubicin administration results in cardiomyopathy and congestive heart failure. In the present study we have established that treatment of rat cardiac myoblasts (H9c2 cells) for 24 hours with doxorubicin resulted in concentration and time dependent cell death as determined by proliferation assay. Almost 50-55% cell death was attained at 24 hours treatment of H9c2 cells with 5 μM doxorubicin. We have selected about 50% cell injury as an optimum doxorubicin-induced cell injury because once this threshold is reached, cells became irreversibly injured and are unable to respond to protective treatment. We have observed that another potent antineoplastic drug, cyclophosphamide, had no cardiotoxic effects even with exposure at 35 μM concentrations for a treatment time of up to 72 hours. Pretreatment of H9c2 cells for 24 hours with 100 nM 17β-estradiol protects about 30% cell death against subsequent treatment for 24 hours with 5 μM doxorubicin. Interestingly 500 nM quecertin and 20 μM resveratrol pretreatment provide about 30% and 40% protection, respectively, to the H9c2 cells against subsequent doxorubicin treatment. However, diethylstilbestrol (DES), bisphenol A, and estrone exhibit no protective effects. It is concluded that 17β-estradiol, resveratrol and quercetin considerably protect H9c2 cells against doxorubicin-induced cell death.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
June 2008
VCU Only:
Off Campus Download
Comments
Part of Retrospective ETD Collection, restricted to VCU only.