Inhibition of 5-lipoxygenase by zileuton in a rat model of myocardial infarction

被引:14
|
作者
Abueid, Leyla [1 ]
Uslu, Unal [4 ]
Cumbul, Alev [4 ]
Ogunc, Ayliz Velioglu [3 ]
Ercan, Feriha [2 ]
Alican, Inci [1 ]
机构
[1] Marmara Univ, Fac Med, Dept Physiol, TR-34854 Istanbul, Turkey
[2] Marmara Univ, Fac Med, Dept Histol & Embryol, Istanbul, Turkey
[3] Marmara Univ, Vocat Sch Hlth Serv, Dept Med Lab Tech, Istanbul, Turkey
[4] Yeditepe Univ, Fac Med, Dept Histol & Embryol, Istanbul, Turkey
来源
ANATOLIAN JOURNAL OF CARDIOLOGY | 2017年 / 17卷 / 04期
关键词
cyclooxygenase; ischemia/reperfusion; myocardial infarction; rat; zileuton; 5-lypoxygenase; ISCHEMIA-REPERFUSION INJURY; CEREBRAL-ISCHEMIA; KNOCKOUT MICE; KAPPA-B; PROSTAGLANDIN; ACTIVATION; APOPTOSIS; CYCLOOXYGENASE-2; BIOSYNTHESIS; INFLAMMATION;
D O I
10.14744/AnatolJCardiol.2016.7248
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 minu-tes 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-alpha), and left ventric-les were excised for evaluation of microscopic damage; malondialdehyde (MDA), glutathione, nuclear factor (NF)-kappa B 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-kappa B 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-alpha levels in I/R group. Conclusion: 5-LOX inhibition in rat myocardial infarction model attenuated increased left ventricle NF-kappa B expression and apoptosis and these actions were not modulated by COX inhibitors.
引用
收藏
页码:269 / 275
页数:7
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