Dexrazoxane does not protect against doxorubicin-induced damage in young rats
| Autor: | Lorraine E. Chalifour, Nicolas Servant, Chunlei Wang, Gordon M. Kirby, Stevan Dostanic, Martin Bernier, Lesley Alpert, Stéphanie Héon |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Heart Diseases Physiology Vesicular Transport Proteins Antineoplastic Agents Pharmacology Rats Sprague-Dawley Proto-Oncogene Proteins Physiology (medical) Internal medicine polycyclic compounds medicine Animals Myocytes Cardiac Doxorubicin bcl-2-Associated X Protein Cardiotoxicity biology Myocardium Body Weight Age Factors Cell Differentiation Organ Size Anticancer drug Rats Oxidative Stress Endocrinology Proto-Oncogene Proteins c-bcl-2 Enzyme inhibitor Apoptosis Heme Oxygenase (Decyclizing) Toxicity biology.protein Female Dexrazoxane Razoxane Cardiology and Cardiovascular Medicine Heme Oxygenase-1 medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 285:H499-H506 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00047.2003 |
| Popis: | Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats. |
| Databáze: | OpenAIRE |
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