Publication: Sıçan miyokard infarktüsü modelinde 5-lipoksijenaz inhibisyonunun etkisi ve siklooksijenaz sistemiyle etkileşimi
Abstract
Amaç: Sıçanda miyokard infarktüsü modelinde 5-lipoksijenaz (LOX) inhibisyonunun tek başına veya siklooksijenaz (COX) inhibitörleriyle birlikte hasar üzerine etkisi araştırılmıştır. Gereç ve Yöntem: Erkek Wistar albino sıçanlara (200-250 g; n=12/ grup) anestezi altında sol ön inen koroner arter (LAD) oklüzyonu ile 30 dakika iskemi ve 120 dakika reperfüzyon, kontrol grubuna yalancı İ/ R uygulanmıştır. Tedavi gruplarına İ/ R’den önce 3 gün süreyle 5-LOX inhibitörü zileuton (Zil; 5 mg/ kg; peroral; günde 2 kez) tek başına veya non-selektif COX inhibitörü indometazin (İndo; 5 mg/ kg; ip), selektif COX-2 inhibitörü nimesulid (Nim); 5 mg/ kg; subkutan) veya selektif COX-1 inhibitörü ketorolak (Ket; 10 mg/ kg; peroral) ile birlikte uygulanmıştır. İ/ R sonrası kanda interlökin (İL)-1beta ve tümör nekroz faktörü (TNF)-alfa düzeyi ölçülmüş, sol ventrikül örneklerinde malondialdehit (MDA), glutatyon (GSH), miyeloperoksidaz (MPO) aktivitesi ölçülmüş; dokular histolojik olarak incelenmiş ve NF-kappaB düzeyi ölçülmüştür. Bulgular: İ/ R grubunda serum sitokin düzeyleri kontrol grubuna göre artmış; ancak tedavili gruplarda İ/ R’ye göre anlamlı bir değişiklik göstermemiştir. İ/ R grubunun doku MPO aktivitesinin kontrol grubundakinden (p<0,05) düşük olduğu görülmüştür; bu etki diğer gruplarda da devam etmiştir. Doku MDA düzeyinin İ/ R grubunda kontrole göre yüksek bulunmuş (p<0,001) ve tedavi gruplarında bu etki devam etmiştir. İ/ R grubuna ait doku GSH düzeyinin kontrol grubuna göre yüksek olduğu ve Zil ile tekrar kontrol seviyelerine döndüğü gözlenmiştir. İ/ R grubunda doku NF-kappaB H-skoru kontrol grubuna göre artmış (p<0,001) ve tedavi gruplarında azalma göstermiştir. Dokuda mikroskopik skor tüm gruplarda kontrol grubuna göre yüksek kalmıştır (p<0,001). Sonuç: Sıçanda miyokard infarktüsü modelinde kalp dokusunda NF-kappaB dışında incelenen diğer oksidan hasar parametrelerinde 5-LOX inhibisyonuyla önemli ölçüde iyileşme gerçekleşmemiştir. Anahtar Sözcükler: Zileuton, lipoksijenaz, siklooksijenaz, miyokard infarktüsü.
The effect of 5-lipoxygenase inhibition and its intraction with cyclooxygenase pathway in a rat model of myocardial infarction Leyla Abueid Objective: Effect of 5-lipoxygenase (LOX) inhibition alone or along with cyclooxygenase (COX) inhibitors in a rat model of myocardial infarction was investigated. Materials and methods: Ischemia and reperfusion (I/ R) was performed in male Wistar rats (200-250 g) with occlusion of the left anterior coronary artery (LAD) for 30 minutes and reperfused for 120 minutes. Treatment groups received 5-LOX inhibitor zileuton (5 mg/ kg; per oral; twice daily) alone or along with the non-selective COX inhibitor indomethacin (5 mg/ kg; intraperitoneally), selective COX-2 inhibitor nimesulide (5 mg/ kg; subcutaneously) or selective COX-1 inhibitor ketorolac (10 mg/ kg; subcutaneously) for 3 days prior to I/ R. Following decapitation, trunk blood was collected for the measurement of cytokines and left ventricles were stored for biochemical analysis and examined microscopically. Results: Serum cytokine levels increased in I/ R group compared to control; however, they did not change significantly in treatment groups. Tissue MPO activity was found to be lower in the I/ R group compared to control (p<0,05); this effect continued in other groups. Tissue MDA of the I/ R group was higher in comparison to control (p<0,001) and this effect contined in treatment groups. High tissue GSH level of the I/ R group in comparison to control was reversed by zileuton. Increased NF-kappaB in I/ R group (p<0,001) was also prevented by all treatments. The microscopic score was higher in all groups compared to control (p<0,001). Conclusion: Oxidant parameters did not seem to be restored by 5-LOX inhibition except for the tissue NF-kappa B level in the rat myocardial infarction model. Key words: Zileuton, lipoxygenase, cyclooxygenase, myocardial infarction.
The effect of 5-lipoxygenase inhibition and its intraction with cyclooxygenase pathway in a rat model of myocardial infarction Leyla Abueid Objective: Effect of 5-lipoxygenase (LOX) inhibition alone or along with cyclooxygenase (COX) inhibitors in a rat model of myocardial infarction was investigated. Materials and methods: Ischemia and reperfusion (I/ R) was performed in male Wistar rats (200-250 g) with occlusion of the left anterior coronary artery (LAD) for 30 minutes and reperfused for 120 minutes. Treatment groups received 5-LOX inhibitor zileuton (5 mg/ kg; per oral; twice daily) alone or along with the non-selective COX inhibitor indomethacin (5 mg/ kg; intraperitoneally), selective COX-2 inhibitor nimesulide (5 mg/ kg; subcutaneously) or selective COX-1 inhibitor ketorolac (10 mg/ kg; subcutaneously) for 3 days prior to I/ R. Following decapitation, trunk blood was collected for the measurement of cytokines and left ventricles were stored for biochemical analysis and examined microscopically. Results: Serum cytokine levels increased in I/ R group compared to control; however, they did not change significantly in treatment groups. Tissue MPO activity was found to be lower in the I/ R group compared to control (p<0,05); this effect continued in other groups. Tissue MDA of the I/ R group was higher in comparison to control (p<0,001) and this effect contined in treatment groups. High tissue GSH level of the I/ R group in comparison to control was reversed by zileuton. Increased NF-kappaB in I/ R group (p<0,001) was also prevented by all treatments. The microscopic score was higher in all groups compared to control (p<0,001). Conclusion: Oxidant parameters did not seem to be restored by 5-LOX inhibition except for the tissue NF-kappa B level in the rat myocardial infarction model. Key words: Zileuton, lipoxygenase, cyclooxygenase, myocardial infarction.