title: Inhibition of 5-lipoxygenase by zileuton in a rat model of myocardial infarction.
abstract: OBJECTIVE
  The goal of the present study was to investigate the effects of 5-lipoxygenase (5-LOX) inhibition, alone and with cyclooxygenase (COX) inhibitors, on inflammatory parameters and apoptosis in ischemia/reperfusion (I/R)-induced myocardial damage in rats. For this purpose, zileuton, a selective and potent inhibitor of 5-LOX, resulting in suppression leukotriene production, was used.
  
  
  METHODS
  Male Wistar rats (200-250 g; n=12 per group) were used in the study. I/R was performed by occluding the left coronary artery for 30 minutes and 2 hours of reperfusion of the heart. Experimental groups were I/R group, sham I/R group, zileuton (5 mg/kg orally, twice daily)+I/R group, zileuton+indomethacin (5 mg/kg intraperitoneally)+I/R group, zileuton+ketorolac (10 mg/kg subcutaneously)+I/R group, and zileuton+nimesulide (5 mg/kg subcutaneously)+I/R group. Following I/R, blood samples were collected to measure tumor necrosis factor alpha (TNF-α), and left ventricles were excised for evaluation of microscopic damage; malondialdehyde (MDA), glutathione, nuclear factor (NF)-κB assays; and evaluation of apoptosis.
  
  
  RESULTS
  Left ventricle MDA in I/R group was higher compared to sham group; however, it did not show significant change with zileuton. Although tissue injury in I/R group was less severe in all treatment groups, it was not statistically significant. NF-κB H-score and apoptotic index, which were higher in I/R group compared to sham I/R, were decreased with application of zileuton (H-score: p<0.01; apoptotic index: p<0.001). Zileuton had no significant effect on increased serum TNF-α levels in I/R group.
  
  
  CONCLUSIONS
  5-LOX inhibition in rat myocardial infarction model attenuated increased left ventricle NF-κB expression and apoptosis and these actions were not modulated by COX inhibitors.
authors.affiliation: Department of Physiology, Faculty of Medicine, Marmara University; İstanbul-Turkey.
authors.forename: Leyla
authors.initials: L
authors.lastname: Abueid
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Yeditepe University; İstanbul-Turkey.
authors.forename: Ünal
authors.initials: Ü
authors.lastname: Uslu
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Yeditepe University; İstanbul-Turkey.
authors.forename: Alev
authors.initials: A
authors.lastname: Cumbul
authors.affiliation: Department of Medical Laboratory Techniques, Vocational School of Health Services, Marmara University; İstanbul-Turkey.
authors.forename: Ayliz
authors.initials: A
authors.lastname: Velioğlu Öğünç
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Marmara University; İstanbul-Turkey.
authors.forename: Feriha
authors.initials: F
authors.lastname: Ercan
authors.affiliation: Department of Physiology, Faculty of Medicine, Marmara University; İstanbul-Turkey. incialican@yahoo.com.
authors.forename: İnci
authors.initials: İ
authors.lastname: Alican
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood / Q000187:drug effects*; D004195:Disease Models, Animal; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D020024:Leukotriene Antagonists; D014409:Tumor Necrosis Factor-alpha; D001094:Arachidonate 5-Lipoxygenase; C063449:zileuton; D006918:Hydroxyurea