Skip Navigation

Cardiovascular Research 2000 46(3):523-530; doi:10.1016/S0008-6363(00)00039-0
© 2000 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Li, T.
Right arrow Articles by Singal, P. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, T.
Right arrow Articles by Singal, P. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2000, European Society of Cardiology

Effects of probucol on changes of antioxidant enzymes in adriamycin-induced cardiomyopathy in rats

Timao Lia,b, Igor Danelisena,b, Adriane Belló-Kleina,b and Pawan K. Singala,b,*

aInstitute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, R2H 2A6, Canada
bDepartment of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, R2H 2A6, Canada

* Corresponding author. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Room R3022, 351 Tache Avenue, Winnipeg, Manitoba, R2H 2A6, Canada. Tel.: +1-204-235-3416; fax: +1-204-233-6723 psingal{at}sbrc.umanitoba.ca

Objective: The clinical usefulness of doxorubicin (adriamycin, ADR) is restricted by the risk of developing congestive heart failure. Probucol has been reported to completely prevent ADR cardiomyopathy without interfering with its antitumor effects. The current study investigated the effects of ADR and probucol on antioxidant enzyme gene expression during adriamycin-induced cardiomyopathy in a rat model. Methods: The mRNA abundance by Northern and immunoreactive protein levels by Western blotting of myocardial antioxidant enzymes, glutathione peroxidase (GSHPx), manganese superoxide dismutase (MnSOD) and catalase (CAT) were examined in relation to the enzyme activities in hemodynamically assessed control and treated animals. Results: At 3 weeks post-treatment duration, ADR caused heart failure which was prevented by probucol. MnSOD mRNA abundance as well as protein levels were depressed by ADR treatment by 45% and 20%, respectively, and this change was prevented by probucol. However, the mRNA and protein levels of GSHPx and CAT were not significantly changed by ADR or probucol. ADR had no effect on SOD activity but this enzyme activity was increased by probucol and probucol plus ADR. GSHPx enzyme activity was decreased and oxidative stress as indicated by TBARS was increased by ADR and these changes were also modulated by probucol. Conclusion: An increase in oxidative stress, GSHPx inactivation and MnSOD downregulation during ADR cardiomyopathy were prevented by probucol treatment.

KEYWORDS Cardiomyopathy; Free radicals; Gene expression; Heart failure; Enzyme (kinetics)


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.