Doxorubicin is one of the most potent anticancer drugs used in the treatment of wide spectrum of neoplastic diseases including breast, thyroid, colon and liver cancer. However, doxorubicin use is associated with undesirable side effects including cardiomyopathy and congestive heart failure. In the present study we have established that treatment of rat cardiac myoblasts (H9c2 cells) with doxorubicin resulted in H9c2 cell injury in a dose and time dependent manner with almost 50% cell death obtained at 5 μM of doxorubicin treatment for 24 hours. We have selected about 50% cell injury as optimum doxorubicin-induced cell injury because once this threshold is reached, cells became irreversibly injured and could not respond to protective treatment. Another potent antineoplastic drug cyclophosphamide had no cardiotoxic effects on H9c2 cells even at 35 μM concentration and up to 72 hours of treatment. Pretreatment of H9c2 cells for 24 hours with dexamethasone, cortisol, corticosterone or progesterone, significantly protect H9c2 myoblasts against subsequent 5 μM doxorubicin treatment for 24 hours in a concentration dependent manner with maximum protection obtained at 100 nM dexamethasone, 100 nM progesterone, 500 nM cortisol and 500 nM corticosterone. However, testosterone or dehydroepiandrosterone had no protective effects even at 10 μM concentration. It is concluded that both glucocorticoids and progesterone protect H9c2 cells against doxorubicin-induced cell injury.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd_retro-1017 |
| Date | 01 January 2006 |
| Creators | AL-Thabhani, Hanaa A. |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Retrospective ETD Collection |
| Rights | © The Author |
Page generated in 0.002 seconds