The Investigation of Effects of Tirofiban on Small Intestine Ischemia and Reperfusion Injury

Abstract

Intestinal ischemia reperfusion (I/R) injury is a significant clinical problem that impacts many remote organ systems, and associated with a high morbidity and mortality. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, shows protective effects on I/R experimental models. The aim of the present study was to investigate the possible effects of tirofiban on intestinal I/R injury.

24 male Wistar albino rats were divided into 3 experimental groups. Rats in the control group (n=8) were subjected to laparotomy without artery occlusion, Rats in the I/R group (n = 8) were subjected to occlusion of superior mesenteric artery for 30 min and 3h reperfusion. Rats in the I/R+Tirofiban group (n = 8) were subjected to I/R and received intravenously 200 μg/kg before reperfusion. At the end of experiment terminal ileum tissues collected and analyzed histopathological changes, lipid peroxidation levels, reduced glutathion (GSH) levels and myeloperoxidase (MPO) activity.

Intestinal tissue histopathological damage scores, the activity of MPO and the level of malondialdehide (MDA) showed a significant increase in the I/R group as compared with the control group. GSH levels showed reduction in the I/R group as compared with the control group. However, I/R+Tirofiban group has no statistically differences as compared with the I/R group for all evaluated parameters.

In conclusion, tirofiban treatment was not able to attaunate or prevent the I/R induced intestinal injury in rats.

Keywords

• Tirofiban,Intestinal Ischemia,Reperfusion Injury

İnce Bağırsak İskemi Reperfüzyon Hasarında Tirofibanın Etkilerinin İncelenmesi

Abstract

İntestinal iskemi reperfüzyon (İ/R) hasarı, çoğu uzak organ sistemini etkileyen ve yüksek morbidite ve mortalite ile ilişkili önemli klinik bir problemdir. Tirofiban; glikoprotein IIb/IIIa reseptör inhibitörüdür ve deneysel İ/R modellerinde koruyucu etkilerinin olduğu gösterilmiştir. Bu çalışmada amacımız tirofibanın intestinal İ/R hasarındaki olası etkilerini incelemektir.

24 adet Wistar Albino sıçan rasgele 3 gruba ayrıldı. Kontrol grubundaki (n=8) sıçanlara arter oklüzyonu yapılmadan yalnızca laparotomi uygulandı. İ/R grubundaki (n=8) sıçanların süperior mezenterik arterine 30 dk oklüzyon ve ardından 3 saat reperfüzyon uygulandı. İ/R+Tirofiban grubundaki (n=8) sıçanlara İ/R uygulandı ve reperfüzyon öncesi intravenöz 200 μg/kg tirofiban verildi. Deney sonunda sıçanların ileum dokuları alındı ve histopatolojik değişiklikler ile lipid peroksidasyon düzeyleri, indirgenmiş glutatyon (GSH) düzeyleri ve miyeloperoksidaz (MPO) aktivitesi değerlendirildi.

İntestinal dokunun histopatolojik hasar skoru, MPO aktivitesi, malondialdehid (MDA) düzeyleri İ/R grubunda kontrol grubuna göre önemli bir artış gösterdi. GSH düzeyi İ/R grubunda kontrol grubuna göre düşük bulundu. Ancak, İ/R+Tirofiban grubu ile İ/R grubu karşılaştırıldığında tüm parametreler için herhangi bir istatistiksel fark saptanmadı.

Sonuç olarak, tirofiban tedavisi İ/R nedenli intestinal hasarı azaltamadı veya önleyemedi.

Keywords

• Tirofiban,İntestinal İskemi,Reperfüzyon Hasarı

References

1. 1. Ueda T, Takagi T, Katada K, Iida T, Mizushima K, Dohi O, Okayama T, Yoshida N, Kamada K, Uchiyama K, Handa O, Ishikawa T, Konishi H, Naito Y, Nagasaki Y, Itoh Y. The protective effect of orally administered redox nanoparticle on intestinal ischemia-reperfusion injury in mice. Biochem Biophys Res Commun 2018; 495(2): 2044-2049.
2. 2. Lin ZL, Tan SJ, Cheng MH, Zhao CY, Yu WK, He YL, Li J, Li N. Lipid-rich enteral nutrition controls intestinal inflammation, improves intestinal motility and mucosal barrier damage in a rat model of intestinal ischemia/reperfusion injury. J Surg Res 2017; 213: 75-83.
3. 3. Turan I, Ozacmak HS, Ozacmak VH, Barut F, Araslı M. Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats. Life Sci 2017; 189: 23-28.
4. 4. Vollmar B, Menger MD. Intestinal ischemia/reperfusion: microcirculatory pathology and functional consequences. Langenbecks Arch Surg 2011; 396(1): 13-29.
5. 5. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia/Reperfusion. Compr Physiol 2016; 7(1): 113-170.
6. 6. Pan G, Long SC, Xu XP, Zhao JH, Li ZZ, Zhang XB, Lu YH, Zhang ZW. Protective Effects of Tirofiban on Myocardial Ischemia-Reperfusion Injury in Rabbits. Am J Ther 2016; 23(6): 1427-1435.
7. 7. Zhou X, Wu X, Sun H, Li J. Efficacy and safety of eptifibatide versus tirofiban in acute coronary syndrome patients: A systematic review and meta-analysis. J Evid Based Med 2017; 10(2): 136-144.
8. 8. Guan W, Wang Z, Liu Y, Han Y, Ren H, Eric Wang W, Yang J, Zhou L, Zeng C. Protective effects of tirofiban on ischemia/reperfusion-induced renal injury in vivo and in vitro. Eur J Pharmacol 2015; 761: 144-152.

9. 9. Karaoglan A, Uçankale M.H, Barut S, Uzun H, Belce A, Çolak A. Neuroprotective Effect of Tirofiban on Temporary Brain Ischemia in Rats: A Preliminary Report. Türk Nörosirürji Dergisi. 2002; 12: 40-47.
10. 10. Chang ST, Chung CM, Chu CM, Yang TY, Pan KL, Hsu JT, Hsiao JF. Platelet Glycoprotein IIb/IIIa Inhibitor Tirofiban Ameliorates Cardiac Reperfusion Injury. Int Heart J 2015; 56(3): 335-340.
11. 11. Liu X, Tao GZ. Effects of tirofiban on the reperfusion-related no-reflow in rats with acute myocardial infarction. J Geriatr Cardiol 2013; 10(1): 52-58.
12. 12. Casini A, Ferrali M, Pampella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol 1986; 123: 520-531.
13. 13. Aykac G, Uysal M, Yalan AS, et al. The effects of chronic ethanol injection on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 1985; 36: 71-76.
14. 14. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78: 206-209.
15. 15. Hierholzer C, Kalff JC, Audolfsson G, Billiar TR, Tweardy DJ, Bauer AJ. Molecular and functional contractile sequelae of rat intestinal ischemia/reperfusion injury. Transplantation 1999; 68(9):1244-54.
16. 16. Tóth Š, Jonecová Z, Čurgali K, Maretta M, Šoltés J, Švaňa M, Kalpadikis T, Caprnda M, Adamek M, Rodrigo L, Kruzliak P. Quercetin attenuates the ischemia reperfusion induced COX-2 and MPO expression in the small intestine mucosa. Biomed Pharmacother 2017; 95: 346-354.
17. 17. Periayah MH, Halim AS, Mat Saad AZ. Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis. Int J Hematol Oncol Stem Cell Res 2017; 11(4): 319-327.
18. 18. Dong W, Chen YD, Qian G, Guo JC, Qi GX, Yang M. The prospective register study of domestic tirofiban for clinical application in acute coronary syndrome. Zhonghua Nei Ke Za Zhi 2013; 52: 815-818.
19. 19. Lapchak PH, Kannan L, Ioannou A, Rani P, Karian P, Dalle Lucca JJ, Tsokos GC. Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol 2012; 302(8): G888-97.
20. 20. Wu MJ, Chen M, Sang S, Hou LL, Tian ML, Li K, Lv FQ. Protective effects of hydrogen rich water on the intestinal ischemia/reperfusion injury due to intestinal intussusception in a rat model. Med Gas Res 2017; 7(2): 101-106.
21. 21. Gonzalez LM, Moeser AJ, Blikslager AT. Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research. Am J Physiol Gastrointest Liver Physiol 2015; 308(2): G63-75.
22. 22. Uysal A, Sahna E, Ozguler IM, Burma O, Ilhan N. Effects of apocynin, an NADPH oxidase inhibitor, on levels of ADMA, MPO, iNOS and TLR4 induced by myocardial ischemia reperfusion. Perfusion 2015; 30(6): 472-477.
23. 23. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 2014; 94(2): 329-354.