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Odemis E, Turkay S, Koca C, et al. Effects of zileuton on the development of autoimmune myocarditis in an experimental rat model. Curr Ther Res Clin Exp. 2007;68(4):262-70doi: 10.1016/j.curtheres.2007.08.002.
Odemis, E., Turkay, S., Koca, C., Kiyici, H., Karadag, A., Bayrak, R., Mete, E., Catal, F., & Yigitoglu, R. (2007). Effects of zileuton on the development of autoimmune myocarditis in an experimental rat model. Current therapeutic research, clinical and experimental, 68(4), 262-70. https://doi.org/10.1016/j.curtheres.2007.08.002
Odemis, Ender, et al. "Effects of zileuton on the development of autoimmune myocarditis in an experimental rat model." Current therapeutic research, clinical and experimental vol. 68,4 (2007): 262-70. doi: https://doi.org/10.1016/j.curtheres.2007.08.002
Odemis E, Turkay S, Koca C, Kiyici H, Karadag A, Bayrak R, Mete E, Catal F, Yigitoglu R. Effects of zileuton on the development of autoimmune myocarditis in an experimental rat model. Curr Ther Res Clin Exp. 2007 Jul;68(4):262-70. doi: 10.1016/j.curtheres.2007.08.002. PMID: 24683216; PMCID: PMC3967347.
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Curr Ther Res Clin Exp. 2007 Jul;68(4):262-70. doi: 10.1016/j.curtheres.2007.08.002.

Effects of zileuton on the development of autoimmune myocarditis in an experimental rat model.

Current therapeutic research, clinical and experimental

Ender Odemis, Sadi Turkay, Cemile Koca, Halil Kiyici, Ahmet Karadag, Reyhan Bayrak, Emin Mete, Ferhat Catal, Ramazan Yigitoglu

Affiliations

  1. Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Fatih University, Ankara, Turkey.
  2. Department of Biochemistry, Faculty of Medicine, Fatih University, Ankara, Turkey.
  3. Department of Pathology, Faculty of Medicine, Baskent University, Konya, Turkey.
  4. Department of Pediatrics, Faculty of Medicine, Fatih University, Ankara, Turkey.
  5. Department of Pathology, Faculty of Medicine, Fatih University, Ankara, Turkey.

PMID: 24683216 PMCID: PMC3967347 DOI: 10.1016/j.curtheres.2007.08.002

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.

Keywords: autoimmunity; leukotrienes; myocarditis; rats; zileuton

References

  1. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 2):S117-9 - PubMed
  2. Clin Immunol Immunopathol. 1990 Nov;57(2):250-62 - PubMed
  3. Am J Pathol. 1984 Jul;116(1):21-9 - PubMed
  4. Circulation. 2006 Feb 14;113(6):876-90 - PubMed
  5. J Immunol. 2005 Jan 15;174(2):589-94 - PubMed
  6. Swiss Med Wkly. 2005 Jun 25;135(25-26):359-64 - PubMed
  7. Curr Opin Cardiol. 2003 May;18(3):175-81 - PubMed
  8. Med J Aust. 2004 Feb 2;180(3):110-2 - PubMed
  9. Jpn Circ J. 2000 Apr;64(4):283-6 - PubMed
  10. Immunology. 2005 Dec;116(4):418-28 - PubMed
  11. Clin Immunol Immunopathol. 1997 May;83(2):93-102 - PubMed
  12. Pharmacol Res. 2005 Dec;52(6):491-6 - PubMed
  13. J Immunol. 2003 Jul 1;171(1):5-10 - PubMed
  14. Postgrad Med J. 2001 Jan;77(903):4-10 - PubMed
  15. Inflammopharmacology. 2006 Mar;14(1-2):10-6 - PubMed
  16. J Am Coll Cardiol. 1997 Nov 1;30(5):1354-9 - PubMed

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