Vitamin D3 and Vitamin D3 Analogs as Protectants Against the Cardiotoxicity of Chemotherapeutic Agents Utilized in the Treatment of Breast Cancer
Abstract
Studies were performed to determine whether 1,25 dihydroxy vitamin D, the active form of this hormone, could protect cardiomyocytes from the toxicity of chemotherapy and radiation. Studies were performed in two models of cardiomyocyte function, H9c2 and HL1 cardiomycoytes. However, 1, 25 dihydroxy vitamin D3 failed to protect against either radiation, adriamycin (doxorubicin) or paclitaxel. We also tested sildenafil as a cardioprotectant, as this phosphodiesterase-5 inibitor has been shown to suppress ischemia -reperfusion injury to the heart. However, neither sildenafil alone nor sildenafil in combination with vitamin D demonstrated significant protection. Subsequent studies indicated that the toxicity of radiation may be related to the promotion of autophagy. In the course of this work, we developed an animal model of radiation induced cardiac injury and studies are ongoing to evaluate other cardioprotective strategies, such as the use of IL-1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA535822
Entities
People
- David A. Gewirtz
Organizations
- Virginia Commonwealth University