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Relationship between gender and cardiotoxicity following doxorubicin treatment in spontaneously hypertensive rats

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • ET Rosen
  • Y Gonzalez-Berrios
  • JS Dickey
  • L Chehab
  • B Aryal
  • EH Herman
  • VA Rao


Cancer treatment with anthracyclines such as doxorubicin (Dox) cause dose-limiting cardiotoxicity, particularly in younger females. Dox metabolites generate excess reactive oxygen species (ROS) via an iron-mediated mechanism in the mitochondria of cardiac cells. Since cardiomyocytes are rich in mitochondria and have lower levels of antioxidant defense, the cardiac cells are uniquely sensitive to ROS. However, the exact reason for gender differences in toxicity is unclear. The aim of our study is to understand gender effects in cardiotoxicity. Our unique model employed female and male adult spontaneously hypertensive rats (SHR) implanted with a breast cancer cell line derived from SHR. After cell implantation, groups of animals were treated with saline, Dox, dexrazoxane, erythropoietin, or combinations with Dox. Tumor size was observed to monitor anticancer activity. Dox showed significant reduction in tumor volume as well as in combination with dexrazoxane and erythropoietin. In addition, cardiac troponin T levels were higher in males treated with Dox than females. Dox increases LC3-II expression in tumor tissue of both males and females, while dexrazoxane and erythropoietin in combination with Dox did not show an increase in LC3-II compared to saline. We are currently testing possible mechanistic links between hormone levels, gender-selective toxicity, and oxidant-induced autophagy.

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