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Indian Journal of Pharmacology
Medknow Publications on behalf of Indian Pharmacological Society
ISSN: 0253-7613
EISSN: 0253-7613
Vol. 42, No. 1, 2010, pp. 44-49
Bioline Code: ph10011
Full paper language: English
Document type: Research Article
Document available free of charge

Indian Journal of Pharmacology, Vol. 42, No. 1, 2010, pp. 44-49

 en Naproxen aggravates doxorubicin-induced cardiomyopathy in rats
Pathan, Rahila Ahmad; Singh, Bhulan Kumar; Pillai, K. K. & Dubey, Kiran

Abstract

Background : The repercussion of the heated dispute on cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) led to the national and international withdrawal of several of the recently introduced coxibs. Further debate and research have highlighted risks of the classical NSAIDs too. There is much controversy about the cardiovascular safety of a nonselective NSAID naproxen (NAP) and its possible cardioprotective effect.
Objectives : The study was undertaken to determine the cardiovascular effects of NAP on doxorubicin-induced cardiomyopathy in rats.
Materials and Methods : Male albino rats received a single i.p. injection of normal saline (normal control group) and doxorubicin (DOX) 15 mg/kg (toxic control group). Naproxen was administered alone (50 mg/kg/day, p.o.) and in combination with DOX and DOX + trimetazidine (TMZ) (10 mg/kg/day, p.o.) for 5 days after 24 h of DOX treatment. DOX-induced cardiomyopathy was assessed in terms of increased activities of serum lactate dehydrogenase (LDH), tissue thiobarbituric acid reactive substances (TBARS) and decreased activities of myocardial glutathione, superoxide dismutase and catalase, followed by transmission electron microscopy of the cardiac tissue.
Results : Doxorubicin significantly increased oxidative stress as evidenced by increased levels of LDH and TBARS and decreased antioxidant enzymes levels. Both biochemical and electron microscopic studies revealed that NAP itself was cardiotoxic and aggravated DOX-induced cardiomyopathy and abolished the protective effect of TMZ in rats.
Conclusions : This study indicates that NAP has the potential to worsen the situation in patients with cardiovascular disease. Therefore, it should be used cautiously in patients with compromised cardiac function.

Keywords
Apoptosis, cardiomyopathy, enzyme (kinetics), free radicals, nonsteroidal anti-inflammatory drugs

 
© Copyright 2010 Indian Journal of Pharmacology.
Alternative site location: http://www.ijp-online.com

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