title: Effects of zileuton on the development of autoimmune myocarditis in an experimental rat model.
abstract: BACKGROUND
  Myocarditis is associated with high morbidity and mortality in childhood, but the pathogenesis of this disease is still unclear. Current knowledge indicates that complex immunopathogenic mechanisms are involved. It is understood that leukotrienes play an important role in the inflammation associated with asthma, and recent reports indicate that leukotrienes participate in immune processes and in autoimmunity.
  
  
  OBJECTIVE
  The aim of this study was to assess the role of leukotriene synthesis in the development of myocardial inflammation and necrosis during myocarditis.
  
  
  METHODS
  The effect of zileuton, a leukotriene synthesis inhibitor, was assessed in an experimental model of autoimmune myocarditis in rats. Healthy adult (10-week-old) male Wistar albino rats were randomly divided into 3 groups. Groups A and B received injections of 1.0 mg porcine cardiac myosin to induce autoimmune myocarditis and group C (the control group) received phosphate-buffered saline. Group B also received zileuton by oral gavage at 100 mg/kg · d(-1). Myocardial inflammation was assessed biochemically via serum concentrations of creatine kinase MB subunit (CK-MB) and troponin T. Cardiac tissue was assessed macroscopically (0 = no inflammation; 1 = a small discolored focus; 2 = diffuse discolored areas covering less than half of the cardiac surface; 3 = diffuse discolored areas covering more than half of the cardiac surface) and microscopically (0 = no inflammation; 1 = ⪯5% infiltration; 2 = 5% to <10% infiltration; 3 = 10% to < 20% infiltration; 4 = >20% infiltration).
  
  
  RESULTS
  Twenty-four rats were divided equally into 3 groups. All rats survived the duration of the study. After 21 days, all rats were euthanized. No significant differences were found between groups A and B in terms of serum concentrations of CK-MB or troponin T. The microscopic pathology score was significantly lower in group B (myosin + zileuton) than in group A (myosin only) (0.12 [0.35] vs 1.25 [1.03]; P = 0.023). The microscopic pathology score was significantly higher in group A than in group C (1.25 [1.03] vs 0; P < 0.01), but the difference between groups B and C was not statistically significant. The macroscopic pathology score was significantly higher in group A than in group B (1.37 [0.91] vs 0.37 [0.51]; P = 0.029). The macroscopic pathology score was significantly higher in group A than in group C (1.37 [0.91] vs 0; P < 0.01). There was no significant difference in macroscopic scores between groups B and C (0.37 [0.51] vs 0).
  
  
  CONCLUSIONS
  In this study of the effects of zileuton in an experimental rat model of autoimmune myocarditis, no significant differences were found in the serum concentrations of the biochemical markers in the 2 groups administered myosin. However, lower macroscopic and microscopic inflammation scores in the zileuton-treated group (group B) compared with the group administered only myosin (group A) suggest that zileuton, a leukotriene-synthesis inhibitor, may suppress the development of experimental autoimmune myocarditis in rats.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Ender
authors.initials: E
authors.lastname: Odemis
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Sadi
authors.initials: S
authors.lastname: Turkay
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Cemile
authors.initials: C
authors.lastname: Koca
authors.affiliation: Department of Pathology, Faculty of Medicine, Baskent University, Konya, Turkey.
authors.forename: Halil
authors.initials: H
authors.lastname: Kiyici
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Karadag
authors.affiliation: Department of Pathology, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Reyhan
authors.initials: R
authors.lastname: Bayrak
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Emin
authors.initials: E
authors.lastname: Mete
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Ferhat
authors.initials: F
authors.lastname: Catal
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Fatih University, Ankara, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Yigitoglu
keywords: autoimmunity; leukotrienes; myocarditis; rats; zileuton