Document Detail


Inhibition of doxorubicin chronic toxicity in catalase-overexpressing transgenic mouse hearts.
MedLine Citation:
PMID:  11800590     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Catalase is an important antioxidant enzyme, which has been shown to provide cardiac protection from acute toxicity induced by doxorubicin, a most effective anticancer agent. Because cumulative dose-dependent chronic cardiomyopathy due to a long-term administration of doxorubicin is a significant clinical problem, the present study was undertaken to test the hypothesis that catalase also provides protection against doxorubicin chronic cardiotoxicity. Transgenic mice containing cardiac catalase activities of 15-, 60-, or 100-fold higher than normal and nontransgenic controls were treated with doxorubicin in a cumulative dose of 45 mg/kg in five equal iv injections (9 mg/kg every other week) over a period of 10 weeks. On the second day after the last injection, the mice were sacrificed for analysis of cardiotoxicity. As compared to nontransgenic controls, doxorubicin-reduced body weight gain was significantly inhibited in the transgenic mice. There were 15% mortality in nontransgenic mice, but no mortality was observed in transgenic mice during the course of treatment. Light microscopic examination revealed that doxorubicin-induced myocardial morphological changes were markedly suppressed in the transgenic mice in an activity-dependent fashion. Under electron microscopy, extensive sarcoplasmic vacuolization and severe disruption of mitochondrial fine structure were observed in nontransgenic cardiomyocytes, but all markedly suppressed in the transgenic mice. The results indicate that catalase elevation in the heart prevents doxorubicin chronic cardiomyopathy.
Authors:
Y James Kang; Xiuhua Sun; Yan Chen; Zhanxiang Zhou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  15     ISSN:  0893-228X     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-21     Completed Date:  2002-03-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Louisville School of Medicine, and Jewish Hospital Heart and Lung Institute, Louisville, KY 40202, USA. yjkang01@athena.louisville.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / toxicity*
Catalase / biosynthesis*,  genetics
Doxorubicin / toxicity*
Heart / drug effects*
Longevity / drug effects
Mice
Mice, Transgenic
Microscopy, Electron
Myocardium / enzymology*,  ultrastructure
Species Specificity
Toxicity Tests
Vacuoles / drug effects,  ultrastructure
Weight Gain / drug effects
Grant Support
ID/Acronym/Agency:
CA68125/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 23214-92-8/Doxorubicin; EC 1.11.1.6/Catalase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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