Document Detail

Melatonin, a pineal hormone with antioxidant property, protects against adriamycin cardiomyopathy in rats.
MedLine Citation:
PMID:  9718077     Owner:  NLM     Status:  MEDLINE    
Adriamycin (ADR) is a potent, broad-spectrum chemotherapeutic agent whose clinical use is limited by its cardiotoxicity. Since the pathogenesis of ADR-induced cardiomyopathy may involve free radicals and lipid peroxidation, the antioxidant, melatonin (MEL) may protect against toxic effects of ADR. We therefore tested this hypothesis using a rat model of ADR-induced cardiomyopathy. Sprague-Dawley rats were given ADR (cumulative dose, 15 mg/kg), MEL (cumulative dose, 84 mg/kg), ADR+MEL, ADR plus probucol (PRB, cumulative dose, 90 mg/kg), or vehicle alone, according to known regimens. The rats were maintained for 3 weeks following treatment, after which their cardiac performance was measured. Following sacrifice, their myocardial ultrastructure was examined, and their myocardial lipid peroxidation was assessed. Mortality was observed only in rats treated with ADR alone. When compared to control rats, surviving rats in the ADR group showed significant decreases in ratio of heart to body weight, arterial pressure, and left ventricular fractional shortening as well as a significant accumulation of ascites. The amount of myocardial thiobarbituric acid reactive substances was significantly higher in ADR-treated than in control rats. Both antioxidants, MEL and PRB, significantly prevented these ADR-induced changes. Electron microscopic examination revealed myocardial lesions indicative of ADR-induced cardiomyopathy in the ADR-treated rats. In contrast, treatment of these rats with MEL or PRB preserved myocardial ultrastructure. By preventing lipid peroxidation, MEL may be highly effective in protecting against ADR-induced cardiomyopathy.
I Morishima; H Matsui; H Mukawa; K Hayashi; Y Toki; K Okumura; T Ito; T Hayakawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  63     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1998  
Date Detail:
Created Date:  1998-09-15     Completed Date:  1998-09-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  511-21     Citation Subset:  IM    
Internal Medicine II, Nagoya University School of Medicine, Japan.
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MeSH Terms
Antibiotics, Antineoplastic / toxicity*
Anticholesteremic Agents / pharmacology
Antioxidants / pharmacology*
Doxorubicin / toxicity*
Heart / drug effects*
Heart Failure / chemically induced*
Lipid Peroxides / metabolism
Melatonin / pharmacology*
Probucol / pharmacology
Rats, Sprague-Dawley
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Anticholesteremic Agents; 0/Antioxidants; 0/Lipid Peroxides; 23214-92-8/Doxorubicin; 23288-49-5/Probucol; 73-31-4/Melatonin

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