title: Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model.
abstract: BACKGROUND
  The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats.
  
  
  OBJECTIVE
  This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats.
  
  
  METHODS
  Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2.5 mg/kg doxorubicin over a period of two weeks. The effect of 28 days of celecoxib (100 mg/kg/day) and its combination with folic acid (10 mg/kg/day) was studied on doxorubicin-induced cardiomyopathy according to serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), troponin-T (Tn-T), tumor necrosis factor alpha (TNF-α), cardiac thiobarbituric acid reactive substance (TBARS), and glutathione (GSH) levels as well as systolic blood pressure (SBP), heart rate (HR) and ultrastructural studies.
  
  
  RESULTS
  Celecoxib cardiotoxicity was manifested by significant increases in the LDH, Tn-T, TNF-α, CK-MB, SBP, HR (p < 0.001) and TBARS (p < 0.01) levels and a significant decrease in the GSH (p < 0.05) level when used alone or administered with doxorubicin. However, the combination of folic acid with celecoxib caused a significant reversal of these parameters and reduced the cardiotoxicity of celecoxib that was aggravated by doxorubicin. The ultrastructural study also revealed myocardial protection with this combination.
  
  
  CONCLUSIONS
  Folic acid protects against the cardiotoxic effects of celecoxib, which are aggravated in the presence of doxorubicin. Folic acid may act as a useful adjunct in patients who are taking celecoxib.
authors.affiliation: a Department of Pharmacology, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.
authors.forename: Shafique
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: b Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.
authors.forename: Bibhu Prasad
authors.initials: BP
authors.lastname: Panda
authors.affiliation: c Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Kohli
authors.affiliation: d Department of Physiology , Hamdard Institute of Medical Sciences and Research, Jamia Hamdard , New Delhi , India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fahim
authors.affiliation: a Department of Pharmacology, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Dubey
mesh_terms: D000818:Animals; D066126:Cardiotoxicity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000068579:Celecoxib / Q000633:toxicity*; D004195:Disease Models, Animal; D005492:Folic Acid / Q000627:therapeutic use*; D006333:Heart Failure / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005492:Folic Acid; D000068579:Celecoxib
keywords: Selective COX-2 inhibitor; TNF-α; Tn-T; cardiovascular