title: Naproxen aggravates doxorubicin-induced cardiomyopathy in rats.
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.
  
  
  OBJECTIVE
  The study was undertaken to determine the cardiovascular effects of NAP on doxorubicin-induced cardiomyopathy in rats.
  
  
  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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Rahila Ahmad
authors.initials: RA
authors.lastname: Pathan
authors.forename: Bhulan Kumar
authors.initials: BK
authors.lastname: Singh
authors.forename: K K
authors.initials: KK
authors.lastname: Pillai
authors.forename: Kiran
authors.initials: K
authors.lastname: Dubey