HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/2/H499    most recent 00047.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Héon, S. Articles by Chalifour, L. E. Search for Related Content PubMed PubMed Citation Articles by Héon, S. Articles by Chalifour, L. E.

Dexrazoxane does not protect against doxorubicin-induced damage in young rats

¹Lady Davis Institute for Medical Research, ²Department of Pathology, and Sir Mortimer B. Davis–Jewish General Hospital, Montréal H3T 1E2; and ³Bank of Montreal Research Center for the Study of Heart Disease in Women, ⁴Department of Biomedical Sciences, University of Guelph, Guelph, N1G 2W1; ⁵Division of Experimental Medicine, McGill University, Montréal, H3A 1A3

Submitted 21 January 2003 ; accepted in final form 17 April 2003

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.

neonate rat; heart; apoptosis; gender

This article has been cited by other articles:

				A. Ascensao, J. Magalhaes, J. M. C. Soares, R. Ferreira, M. J. Neuparth, F. Marques, P. J. Oliveira, and J. A. Duarte Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H722 - H731. [Abstract] [Full Text] [PDF]