Myokardiyal iskemi reperfüzyon sonrası böbrek hasarında nitrik oksit'in rolü ve caffeic acid phenethyl ester (cape)'in etkisi

Year 2005, Volume: 12 Issue: 4, 23 - 27, 16.04.2009

Mehmet Özer Ekrem Çiçek Osman Gökalp Ahmet Koyu Hakan Parlakpınar Ahmet Acet

Abstract

SüleymanDemirel Üniversitesi
TIP FAKÜLTESİ DERGİSİ: 2005 Aralık; 12(4)



Myokardiyal iskemi reperfüzyon sonrası böbrek hasarında nitrik oksit'in rolü ve caffeic acid phenethyl ester (cape)'in etkisi


Mehmet Kaya Özer, Ekrem Çiçek, Osman Gökalp,
Ahmet Koyu, Hakan Parlakpınar, Ahmet Acet



Özet

Myokardiyal iskemi-reperfüzyon (MI/R) sırasında perifere giden kan akımında bir değişiklik olduğu bilinmektedir. Bu durum fazla kanlanan organlardan biri olan böbreklerde hasara neden olmakta ve oluşan bu hasar myokardiyal revaskülarizasyon ve benzeri kalp cerrahisinin yararlarını azaltmaktadır. Sözkonusu olan bu böbrek hasarın nedenleri çok çeşitli olmakla birlikte, revaskülarizasyon sırasında hipoperfüzyon, pulsatil perfüzyonun kaybolması, hemoliz ve sistemik inflamatuvar yanıt gibi faktörlerin etkili olduğu belirtilmiştir. Buna ek olarak, direkt yapılan böbrek iskemi reperfüzyonunda meydana gelen nitrik oksid (NO)'in süperoksit (O2-) radikali ile birleşerek meydana getirdiği peroksinitrit (ONOO-) bu hasarın meydana gelmesinde önemli bir role sahip olduğu bildirilmiştir. Bu çalışmada MI/R ile oluşan böbrek perfüzyon değişikliklerinde, hasarla ilişkili olduğu sanılan NO düzeyi üzerine antioksidan Caffeic acid phenethyl ester (CAPE)'in etkisi araştırıldı. Yirmi bir yetişkin erkek Wistar sıçan kullanıldı. Hayvanlar; kontrol, MI/R ve CAPE+MI/R olmak üzere üç gruba ayrıldı. MI/R ve CAPE+MI/R grubundaki sıçanların sol koroner arteri 30 dakika süreyle kapatıldı (iskemi) ve 120 dakika süreyle de tekrar açıldı (reperfüzyon). CAPE+MI/R grubunda bulunan sıçanlara iskemiden on dakika önce başlanılarak reperfüzyon başlangıcına kadar CAPE (50 ìmol kg-1), perfüzyon pompasıyla uygulandı. Reperfüzyon sonrası böbrekler alınarak NO düzeyleri ve histolojik değişiklikler araştırıldı. MI/R grubu sıçanların böbreklerinde kontrol grubuna göre NO düzeyinde istatistiksel olarak anlamlı bir artış gözlendi (p<0.05). CAPE MI/R'ın neden olduğu böbrek NO düzeyindeki artışı önledi. Histopatolojik sonuçların da bu durumu desteklediği görüldü. Sonuç olarak, MI/R'ın periferdeki kan perfüzyonunu değiştirerek böbreklerde NO düzeyini artırdığı, kalp cerrahisinde meydana gelen böbrek bozukluklarında muhtemelen NO düzeyindeki aşırı artışın da rol oynadığını ve bu zararlı etkinlerin CAPE ile önlenebileceğini söyleyebiliriz.



Anahtar kelimeler: Myokardiyal iskemi reperfüzyon, böbrek, nitrik oksit, Caffeic acid phenethyl ester (CAPE)



Abstract



Role of nıtrıc oxıde ın the renal damage after myocardıal ıschemıa reperfusıon and effect of caffeıc acıd phenethyl ester (cape)

It is known that there is a change peripheral blood flow during myocardial ischemia-reperfusion (MI/R). This situation causes damage in the kidneys which are one of the much perfusing organs. The above mentioned damage occurring in the kidneys reduces use of myocardial revascularization and such like heart surgery. However, even though the reasons of this kidney damage are various, it has been informed that it depends on factors such as hypoperfusion, disappearing of pulsatile perfusion, hemolysis and systemic inflammatory reply during revascularization. In addition, it has been informed that it is effective in the damage that nitric oxide (NO) combines with superoxid radical (O2-) and forms peroxinitrit (ONOO-) in the kidney with ischemia reperfusion done directly. In the our study, we studied the effect of antioxidant Caffeic acid phenethyl ester (CAPE) on NO level which is thought to be related with the damage occurring kidney perfusion changes due to myocardial ischemia reperfusion (MI/R). Twenty one adult male Wistar rats were divided into tree groups as control, MI/R and CAPE+MI/R. The left coroner artery was occluded for 30 min and then reperfused for 120 min more before the experiment was terminated in the MI/R and CAPE+MI/R groups, and CAPE (50 mol kg-1) was administered 10 min prior to ischemia and during occlusion by infusion in the CAPE group. At the end of the reperfusion period, rats were sacrificed, and the kidneys were quickly removed for NO determination and histopathological analysis. Compared with control, MI/R was accompanied by a significant increase in NO production in the rat kidney. Administration of CAPE reduced NO production in the kidney. These beneficial changes in these biochemical parameters were also associated with parallel changes in histopathological appearance. Consequently, MI/R changes peripheral blood perfusion and increases NO level in the kidneys and thus, the excessive increase in NO level probably also plays a role in renal disorders during heart surgery. We can say that these harmful effects can be prevented by means of CAPE.



Key words: Myocardial ischemia reperfusion, kidney, nitric oxide, Caffeic acid phenethyl ester (CAPE)

Keywords

Myokardiyal iskemi reperfüzyon, böbrek, nitrik oksit, Caffeic acid phenethyl ester (CAPE)

References

• Sahna E, Parlakpinar H, Cihan OF, Turkoz Y, Acet A. Effects of aminoguanidine against renal ischaemia- reperfusion injury in rats. Cell Biochem Funct. 2004;22: [Epub ahead of print]
• Sahna E, Parlakpinar H, Ozturk F, Cigremis Y, Acet A. The protective effects of physiological and pharmacological concentrations of melatonin on renal ischemia-reperfusion injury in rats. Urol Res. 2003:31(3):188-193.
• Ozyurt H, Irmak MK, Akyol O, Sogut S. Caffeic acid phenethyl ester changes the indices of oxidative stress in serum of rats with renal ischaemia-reperfusion injury. Cell Biochem Funct. 2001;19(4):259-263.
• Ozer MK, Parlakpinar H, Acet A. Reduction of ischemia-reperfusion induced myocardial infarct size in rats by caffeic acid phenethyl ester (CAPE). Clin Biochem. 200;37(8):702-705.
• Sud’ina GF, Mirzoeva OK, Puskareva MA, et al. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett 1993;329:21.
• Boldt J, Brenner T, Lang J, Kumle B, Isgro F. Kidney- specific proteins in elderly patients undergoing cardiac surgery with cardiopulmonary bypass. Anesth Analg. 2003 Dec;97(6):1582-1589.
• Loef BG, Epema AH, Navis G, Ebels T, van Oeveren W, Henning RH. Off-pump coronary revascularization attenuates transient renal damage compared with on- pump coronary revascularization. Chest. 2002;121(4):1190-1194.
• Stallwood MI, Grayson AD, Mills K, Scawn ND. Acute renal failure in coronary artery bypasses surgery: independent effect of cardiopulmonary bypass. Ann Thorac Surg. 2004;77(3):968-972.
• Loef BG, Henning RH, Epema AH, Rietman GW, van Oeveren W, Navis GJ, Ebels T. Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass. Br J Anaesth. 2004;93(6):793-798.
• Ferdinandy P, Schulz R. Nitric oxide, superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury and preconditioning. Br J Pharmacol. 200;138(4):532- 543
• Ronson RS, Nakamura M, Vinten-Johansen J. The cardiovascular effects and implications of peroxynitrite. Cardiovasc Res. 1999;44(1):47-59.
• Beckman JS. -OONO: rebounding from nitric oxide. Circ Res. 2001 Aug 17;89(4):295-297.
• Ozer MK, Sahna E, Birincioglu M, Acet A. Effects of captopril and losartan on myocardial ischemia–reperfusion induced arrhythmias and necrosis in rats. Pharmacol Res 2002;45(4):257– 263.
• Sahna E, Acet A, Ozer MK, Olmez E. Myocardial ischemia– reperfusionin rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin. J Pineal Res 2002;33(4):234– 238.
• Walker MJ, Curtis MJ, Hearse DJ, Campbell RW, Janse MJ, Yellon DM, Cobbe SM, Coker SJ, Harness JB, Harron DW, et al. The Lambeth conventions: guidelines for the study of arrhythmias in ischemia infarction, and reperfusion. Cardiovasc Res 1988; 22: 447–455.
• Adams LB, Hibbs JB Jr, Taintor RR, Krahenbuhl JL. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990;144(7):2725-2729.
• James JP, Benedict RL. Mechanism of myocardial reperfusion injury. Ann Thorac Surg 1999;68:1905- 1912
• Parlakpinar H, Tasdemir S, Polat A, Bay-Karabulut A, Vardi N, Ucar M, Acet A. Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats. Toxicology. 2005;207(2):169-177.
• Yagmurca M, Erdogan H, Iraz M, Songur A, Ucar M, Fadillioglu E. Caffeic acid phenethyl ester as a protective agent against doxorubicin nephrotoxicity in rats. Clin Chim Acta. 2004;348(1-2):27-34