Börteçin EYGİ, Habib ÇAKIR, Köksal DÖNMEZ, Şahin İŞCAN, İhsan PEKER, Fatmagül KUŞKU, Ali GÜRBÜZ, İsmail YÜREKLİ

Silostazol ve rosuvastatinin böbrek ve kalp üzerine etkilerinin araştırılması: Deneysel akut böbrek ve kalp hasarı modeli

Amaç: Bu çalışmada, deneysel bir modelde ameliyat öncesi silostazol ve rosuvastatin tedavisinin böbrek iskemi/reperfüzyon hasarına olan etkisi ve uzak kalp reperfüzyon hasarı üzerine olan etkisi araştırıldı. Çalışma planı: Toplam 35 adet dişi Sprague-Dawley sıçan rastgele beş gruba ayrıldı (n=7). Median laparotomi yapılarak, her iki böbreğe 45 dakika süren iskemi uygulandı. Cerrahi girişimin üç gün öncesinden başlayarak oral tedavi uygulandı (20 mg/kg silostazol, 10 mg/kg rosuvastatin ve 20 mg/kg cilostazol + 10 mg/kg rosuvastatin). Cerrahi girişimden bir gün sonra ise kan örnekleri ve böbrek ve kalp doku örnekleri alındı. Bulgular: Böbrek dokularının immünhistokimyasal değerlendirmesinde tümör nekroz faktör-alfa ve hipoksi ile indüklenebilir faktör-1 alfa immünreaktivitesinin silostazol, rosuvastatin ve silostazol + rosuvastatin grubunda, iskemi/ reperfüzyon hasarı grubuna kıyasla anlamlı düzeyde daha düşük olduğu tespit edildi (p

Investigation the effects of cilostazol and rosuvastatin on kidney and heart: An experimental acute kidney and heart injury model

Background: In this study, we aimed to assess the effects of preoperative cilostazol and rosuvastatin therapy on kidney ischemia/ reperfusion injury and remote cardiac reperfusion injury in an experimental model.Methods: A total of 35 female Sprague-Dawley rats were randomly divided into five groups (n=7). Median laparotomy and a 45-min bilateral kidney ischemia were performed. Oral medications were administered three days before the surgical intervention (20 mg/kg cilostazol, 10 mg/kg rosuvastatin and 20 mg/kg cilostazol + 10 mg/kg rosuvastatin). Blood samples and kidney and heart tissue samples were extracted one day after surgery.Results: Immunohistochemical examination of the kidney samples revealed that tumor necrosis factor- alpha and hypoxia-inducible factor-1 alpha immunoreactivities in the cilostazol, rosuvastatin, and cilostazol + rosuvastatin groups were found to be signifiicantly lower, compared to ischemia/reperfusion injury group (p

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24. Jones SP, Gibson MF, Rimmer DM, Gibson TM, Sharp BR, Lefer DJ. Direct vascular and cardioprotective effects of rosuvastatin, a new HMG -CoA reductase inhibitor. J Am Coll Cardiol 2002;40:1172-8.
23. Wu Y, Wang Y, An C, Dong Z, Liu H, Zhang Y, et al. Effects of rosuvastatin and atorvastatin on renal function: meta-analysis. Circ J 2012;76:1259-66.
22. Weinberg EO, Scherrer-Crosbie M, Picard MH, Nasseri BA, MacGillivray C, Gannon J, et al. Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion. Am J Physiol Heart Circ Physiol 2005;288:1802-9.
21. Qiao B, Deng J, Li Y, Wang X, Han Y. Rosuvastatin attenuated contrast-induced nephropathy in diabetes patients with renal dysfunction. Int J Clin Exp Med 2015;8:2342-9.
20. Layton JB, Hansen MK, Jakobsen CJ, Kshirsagar AV, Andreasen JJ, Hjortdal VE, et al. Statin initiation and acute kidney injury following elective cardiovascular surgery: a population cohort study in Denmark†. Eur J Cardiothorac Surg 2016;49:995-1000.
19. Jiang F, Yang J, Zhang L, Li R, Zhuo L, Sun L, et al. Rosuvastatin reduces ischemia-reperfusion injury in patients with acute coronary syndrome treated with percutaneous coronary intervention. Clin Cardiol 2014;37:530-5.
18. Ragab D, Abdallah DM, El-Abhar HS. Cilostazol renoprotective effect: modulation of PPAR-, NGAL, KIM-1 and IL-18 underlies its novel effect in a model of ischemia-reperfusion. PLoS One 2014;9:95313.
17. Moreira Neto AA, Souza Júnior SS, Capelozzi VL, Parra-Cuentas ER, Schmidt Júnior AF, Francisco Neto A, et al. Effects of cilostazol in kidney and skeletal striated muscle of Wistar rats submitted to acute ischemia and reperfusion of hind limbs. Acta Cir Bras 2012;27:783-8.
16. Frias Neto CA, Koike MK, Saad KR, Saad PF, Montero EF. Effects of ischemic preconditioning and cilostazol on muscle ischemia-reperfusion injury in rats. Acta Cir Bras 2014;29:17-21.
15. Frias Neto CA, Koike MK, Saad KR, Saad PF, Montero EF. Effects of ischemic preconditioning and cilostazol on muscle ischemia-reperfusion injury in rats. Acta Cir Bras 2014;29:17-21.
14. Ball T, McCullough PA. Statins for the prevention of contrast-induced acute kidney injury. Nephron Clin Pract 2014;127:165-71.
13. Gokce M, Yuzbasioglu MF, Bulbuloglu E, Oksuz H, Yormaz S, Altınoren O, et al. Cilostazol and diltiazem attenuate cyclosporine-induced nephrotoxicity in rats. Transplant Proc 2012;44:1738-42.
12. Tai ST, Fu YH, Yang YC, Wang JJ. Niacin ameliorates kidney warm ischemia and reperfusion injury-induced ventricular dysfunction and oxidative stress and disturbance in mitochondrial metabolism in rats. Transplant Proc 2015;47:1079-82.
11. Hansen MK, Gammelager H, Jacobsen CJ, Hjortdal VE, Layton JB, Rasmussen BS, et al. J Cardiothorac Vasc Anesth 2015;29:617-25.
10. Martin GS, Becker BN, Schulman G. Cardiac troponin-I accurately predicts myocardial injury in renal failure. Nephrol Dial Transplant 1998;13:1709-12.
9. Khandoga A, Enders G, Biberthaler P, Krombach F. Poly(ADP- ribose) polymerase triggers the microvascular mechanisms of hepatic ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 2002;283:553-60.
8. Di Napoli P, Antonio Taccardi A, Grilli A, Spina R, Felaco M, Barsotti A, et al. Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: an ex vivo study in isolated working rat hearts. Cardiovasc Res 2001;51:283-93.
7. Wakida K, Morimoto N, Shimazawa M, Hozumi I, Nagase H, Inuzuka T, et al. Cilostazol reduces ischemic brain damage partly by inducing metallothionein-1 and -2. Brain Res 2006;1116:187-93.
6. Hashimoto A, Miyakoda G, Hirose Y, Mori T. Activation of endothelial nitric oxide synthase by cilostazol via a cAMP/ protein kinase A- and phosphatidylinositol 3-kinase/Akt-dependent mechanism. Atherosclerosis 2006;189:350-7.
5. Manickavasagam S, Ye Y, Lin Y, Perez-Polo RJ, Huang MH, Lui CY, et al. The cardioprotective effect of a statin and cilostazol combination: relationship to Akt and endothelial nitric oxide synthase activation. Cardiovasc Drugs Ther 2007;21:321-30.
4. Gülmen Ş, Doğuç DK, Ceylan BG, Çetin NK, Meteoğlu İ, Okutan H, et al. The effect of beta-glucan on kidney injury in experimental aortic ischemia -reperfusion. Turkish J Thorac Cardiovasc Surg 2011;19:234-41.
3. Youssef MI, Mahmoud AA, Abdelghany RH. A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/ reperfusion in rats. Biochem Pharmacol 2015;96:20-9.
2. Burne-Taney MJ, Kofler J, Yokota N, Weisfeldt M, Traystman RJ, Rabb H. Acute renal failure after whole body ischemia is characterized by inflammation and T cell-mediated injury. Am J Physiol Renal Physiol 2003;285:87-94.
1. Lafrance JP, Miller DR. Acute kidney injury associates with increased long-term mortality. J Am Soc Nephrol 2010;21:345-52.