Prevention by dexrazoxane of down-regulation of ryanodine receptor gene expression in anthracycline cardiomyopathy in the rat.

Abstract:

:Anthracyclines can cause cumulative dose-related cardiotoxicity characterized by changes in Ca(2+) metabolism, including dysfunction of the sacroplasmic reticulum (SR) and decreased expression of Ca(2+)-handling proteins, such as the ryanodine receptor (RyR2). In this study, we examined the effect of dexrazoxane (ICRF-187), an iron chelator which prevents anthracycline cardiotoxicity, on RyR2 gene expression in rats treated chronically with daunorubicin. Daunorubicin (2.5 mg kg(-1) i.v. weekly for 6 weeks) produced cardiotoxicity as demonstrated by histopathologic changes. The ryanodine receptor/glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA ratio was decreased by 38+/-3% (P<0.02) compared to values in control rats. Dexrazoxane pre-treatment (50 mg kg(-1); 1 h prior to each daunorubicin injection) prevented the decrease in RyR2/GAPDH mRNA ratio and histopathologic lesions in daunorubicin-treated rats. This is the first report that a protective agent such as dexrazoxane can ameliorate the decreased expression of a specific gene involved in anthracycline-induced cardiotoxicity.

journal_name

Br J Pharmacol

authors

Burke BE,Gambliel H,Olson RD,Bauer FK,Cusack BJ

doi

10.1038/sj.bjp.0703538

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

1-4

issue

1

eissn

0007-1188

issn

1476-5381

journal_volume

131

pub_type

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