Ali Doğan DURSUN, Mustafa ARSLAN, Ayşegül KÜÇÜK, Dilek ERER, Abdullah ÖZER, Yücel POLAT

Streptozosin ile Diyabet Oluşturulan Ratlarda Pikrozid II’nin Miyokard İskemi Reperfüzyon Hasarı Üzerine Etkisi

Amaç: Diyabetes mellitus, oksidatif stres artışının eşlik ettiği kronik metabolik bir hastalıktır. İskemi-reperfüzyon (İ/R) hasarı doku iskemisi tarafından başlatılan olayların bir kaskadıdır. Reperfüzyon sonucunda oluşan hücre hasarı inflamatuar yanıtı aktive eder. Bu çalışma, Streptozosin kaynaklı diyabeti olan ratlarda miyokard İ/R hasarı üzerine Pikrozid II’nin etkisini araştırmak amacıyla yapıldı. Yöntem: Hayvanlar, beş gruba (n=6) olacak şekilde ayrıldı; Kontrol grubu (K), Diyabet grubu [D], Diyabet + Pikrozid II grubu [DP], Diyabet + İ/R grubu [DİR] ve Diyabet + İ/R + Pikrozid II grubu [DİRP]. DİR grubunda, sol ön inen arter dalı iskemi amaçlı 60 dakika süre ile kapatılmış ardından reperfüzyon için akım sağlanarak 120 dakika beklenmiştir. DİRP grubuna sol ön inen arter dalı kapatılmadan 30 dakika önce Pikrozid II, 10 mg/kg olmak üzere intraperitoneal olarak verildi. Çalışmanın sonunda, miyokard doku örnekleri total oksidan durum ve total antioksidan durum seviyesinin ölçülmesi için alındı. Bulgular: Toplam oksidan durum seviyeleri DİR grubunda, diğer gruplarla karşılaştırıldığında (K, DP, DİRP) anlamlı yüksek bulunmuştur (sırasıyla p:0.001, p:0.019, ve p:0.031). Total antioksidan durum seviyeleri DİR grubunda, diğer gruplarla karşılaştırıldığında (K, DP, DİRP ) anlamlı olarak yüksek bulunmuştur (sırasıyla p:0.006, p:0.024, ve p:0.007). Sonuç: Bu bulgular Pikrozid II’nin İ/R hasarına karşı koruyucu etkiye sahip olabileceğini göstermektedir.

Effects of Picroside II on Myocardial Ischemia-Reperfusion Injury in Streptozotocin-Induced Diabetic Rats

Objective: Diabates mellitus, is a chronic metabolic disorder accompanied byan increase in oxidative stress. Ischemia-reperfusion injury is a cascade ofevents initiated by tissue ischemia. The cellular damage produced byreperfusion leads to an active inflammatory response. This study wasperformed to investigate the effect of picroside II on myocardial ischemiareperfusioninjury in rats with streptozotocin-induced diabetes.Methods: Animals were equally (n:6) divided for five groups as follows;Control (C), diabetes [D], diabetes+picroside II [DP], diabetes+I/R [DIR], anddiabetes+I/R+ picroside II [DIRP]. In DIR group, a left anterior descendingartery branch was occluded for 60 minutes, the reperfused for 120 minutes.In DIRP group, picroside II was administrated via 10 mg/kg intraperitonealroute 30 minutes before ligating the left anterior descending artery. At theend of the study, myocardial tissues were taken for total oxidant status andtotal antioxidant status level determinations.Results: Total oxidant status levels were significantly higher in DIR group,when compared with C, DP, and DIRP groups (p:0.001, p:0.019, and p:0.031,respectively). Total antioxidant status levels were significantly higher in DIRgroup, when compared with C, DP, and DIRP groups (p:0.006, p:0.024, andp:0.007, respectively).Conclusion: These results indicate that administration of picroside II mayhave protective effects against I/R injury.

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Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3: e442.
Hensley K, Robinson KA, Gabbita SP, et al. Reactive oxygen species, cell signaling, and cell injury. Free Radic Biol Med 2000; 15;28: 1456-62.
Pitkanen OM, Martin JM, Hallman M, et al. Free radical activity during development of insulin dependent diabetes mellitus in the rat. Life Science 1992; 50: 335-9.
Bhat WW, Dhar N, Razdan S, et al. Molecular characterization of UGT94F2 and UGT86C4, two glycosyltransferases from Picrorhiza kurrooa: comparative structural insight and evaluation of substrate recognition. PLoS ONE 2013; 8 e73804.
Sood H, Chauhan RS. Biosynthesis and accumulation of a medicinal compound, Picroside-I, in cultures of Picrorhiza kurroa Royle ex Benth. Plant Cell Tiss Organ Cult 2010; 100: 113–7.
Ansari RA, Aswal BS, Chander R, et al. Hepatoprotective activity of kutkin—the iridoid glycoside mixture of Picrorhiza kurroa. Indian Journal of Medical Research. 1988; 87: 401–4.
Banerjee D, Maity B, Nag SK, et al. Healing potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration. BMC Complement Altern Med 2008; 31;8:3.
Rajkumar V, Guha G, Kumar RA. Antioxidant and anti-neoplastic activities of Picrorhiza kurroa extracts. Food Chem Toxicol 2011; 49: 363–9.
Sud A, Chauhan RS, Tandon C. Identification of imperative enzymes by differential protein expression in Picrorhiza kurroa under metabolite accumulating and nonaccumulating conditions. Protein Pept Lett 2013; 20: 826–5.
Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-11.
Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277-85.
Jennings RB, Sommers HM, Smyth GA, Flack HA, Linn H. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol 1960; 70: 68–78.
Mozaffari MS, Liu JY, Abebe W, Baban B. Mechanisms of load dependency of myocardial ischemia reperfusion injury. Am J Cardiovasc Dis 2013;3: 180–96.
Turer AT, Hill JA. Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy. Am J Cardiol 2010; 106:360–8.
Cohen MV, Yang XM, Downey JM. The pH hypothesis of postconditioning: Staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation 2007;115: 1895–903.
Ji Y, Pang QF, Xu G, Wang L, Wang JK, Zeng YM. Exogenous hydrogen sulfide postconditioning protects isolated rat hearts against ischemia-reperfusion injury. Eur. J.Pharmacol 2008; 587:1–7.
Oyar EO, Kiris I, Gulmen S, et al. The protective effect of adrenomedullin on renal injury, in a model of abdominal aorta cross-clamping. Thorac Cardiovasc Surg 2012; 60:5-10.
Kiraz HA, Poyraz F, Kip G, et al. The effect of levosimendan on myocardial ischaemia reperfusion injury in streptozotocin induced diabetic rats. Libyan J Med 2015 Dec 7;10:29269. doi: 10.3402/ljm.v10.29269. eCollection 2015.
Arslan M, Poyraz F, Kiraz HA, et al. The effect of dexmedetomidine on myocardial ischaemia reperfusion injury in streptozotocin induced diabetic rats. Anaesth Pain & Intensive Care 2015; 19: 444-51.
Chang Z. Role of toll-like receptors in regulatory functions of T and B cells. Chinese Science Bulletin 2008; 53(8): 1121–7.
Liu G, Zhang L, Zhao Y. Modulation of immune responses through direct activation of Toll-like receptors to T cells. Clin Exp Immunol 2010;160: 168–75.
Wang L, Liu XH, Chen H, Chen ZY, Weng XD, Qiu T, Liu L. Picroside II protects rat kidney against ischemia/reperfusion-induced oxidative stress and inflammation by the TLR4/NF-κB pathway. Exp Ther Med 2015; 9: 1253-8.
Wu N, Li W, Shu W, et al. Protective effect of picroside II on myocardial ischemia reperfusion injury in rats. Drug Des Devel Ther 2014 May 14; 8:545-54
Fantone JC, Kinnes DA. Prostaglandin E1 and prostaglandin I2 modulation of superoxide production by human neutrophils. Biochem Biophys Res Commun 1983; 113: 506-12.
Simpson PJ, Mickelson J, Fantone JC, et al. Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart. Circ Res 1987; 60: 666- 73.
Kiris I, Tekin I, Yilmaz N, et al. Iloprost downregulates expression of adhesion molecules and reduces renal injury induced by abdominal aortic ischemia-reperfusion. Ann Vasc Surg 2009; 23: 212-23.
Bursch W, Taper HS, Somer MP, et al. Histochemical and biochemical studies on the effect of the prostacyclin derivative Iloprost on CCl4-induced lipid peroxidation in rat liver and its significance for hepatoprotection. Hepatology 1989;9: 830-8.
Yu AL, Fuchshofer R, Kampik A, et al. Effects of oxidative stress in trabecular meshwork cells are reduced by prostaglandin analogues. Invest Ophthalmol Vis Sci 2008; 49: 4872- 80.
Gao H, Zhou YW. Anti-lipid peroxidation and protection of liver mitochondria against injuries by picroside II. World J Gastroenterol 2005; 11(24): 3671-4.