The Effects of Apelin on Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Model

Yıl 2012, Cilt: 2012 Sayı: 2, 148 - 152, 01.02.2012

Tamer Sağıroğlu Serhat Oğuz Gönül Sağıroğlu Tulin Yalta Elif Çopuroğlu Mustafa Burak Sayhan Mehmet Ali Yağcı

https://doi.org/10.5152/balkanmedj.2011.036

Öz

Objective: Intestinal ischemia-reperfusion (I/R) injury is associated with high morbidity and mortality rates. There is ongoing research to find an effective preventive or treatment agent. We aimed to evaluate the effects of apelin 13 (AP) on intestinal I/R injury in a rat model. Material and Methods: Twenty-four male Sprague-Dawley rats aged 6-8 weeks and weighing 280±20 g were equally divided into three groups (control, I/R and I/R+AP). The control group underwent superior mesenteric artery (SMA) mobilization alone without any clamping. In the I/R and I/R+AP groups, an atraumatic microvascular bulldog clamp was placed across the SMA at its point of origin from the aorta. In the I/R+AP group, 2 μg/kg/d apelin was administered intraperitoneally. After 60 minutes of ischemia, relaparotomy was performed to remove the microvascular clamp on the SMA for 3 hours of reperfusion. After 3 hours, tissue samples were obtained for biochemical [malondialdehyde (MDA) and glutathione (GSH) levels] and histopathological analyses. Results: MDA levels were significantly higher in the I/R group compared to the control group. Although MDA levels were lower in the I/R+AP group compared tothe I/R group, the difference was not statistically significant. There was also no significant difference between the I/R+AP and I/R groups regarding GSH levels. The median histopathological grade was significantly lower in the I/R+AP group compared to the I/R group (p=0.001). Conclusion: Apelin appeared to have a positive effect on oxidative injury; this did not reach statistical significance. Thus, the role of apelin and associated findings in the initial treatment of intestinal ischemia needs further large-scale animal studies before human use. Turkish Başlık: Deneysel Sıçan Modeli Mezenterik İskemi ve Reperfüzyon Hasarında Apelinin Etkileri Anahtar Kelimeler: Apelin, mezenterik iskemi, reperfüzyon hasarı Amaç: Barsak iskemi-reperfüzyon (I/R) hasarı yüksek morbidite ve mortalite oranları ile seyreder. Etkili koruyucu veya tedavi edici ajanlar bulmak için sürekli araştırmalar yapılmaktadır. Barsak İ/R hasarının sıçan modelinde apelin 13 (AP)'ün etkilerini araştırmayı amaçladık. Çalışma Planı: 6-8 haftalık ve 280±20 g ağırlığında 24 adet erkek Sprague Dawley sıçan eşit olarak üç gruba ayrıldı (Kontrol, I/R ve I/R+AP). Kontrol grubuna klemp uygulanmadan süperiyor mezenterik arter (SMA) ayrıldı. I/R ve I/R+AP gruplarında atravmatik mikrovazküler bulldog klemp SMA nın aortadan çıkış noktasına yerleştirildi. 60 dk iskemiden sonra, klempler alınarak 3 saat reperfüzyon uygulandı. 3 saat Reperfüzyondan sonra, biyokimyasal incelemeler (malondialdehit (MDA) ve glutatyon (GSH) düzeyleri) ve histopatolojikal incelemeler için doku örnekleri alındı. Bulgular: Kontrol grubu ile karşılaştırıldığında MDA düzeyleri I/R grubunda anlamlı düzeyde yüksekti. MDA düzeyleri I/R grubu ile karşılaştırıldığında I/R+AP grubunda düşük olmasına rağmen, farklılık anlamlı değildi. I/R ile I/R+AP grupları arasında GSH düzeyleri arasında anlamlı farklılık yoktu. I/R+AP grubu histopatolojik medyan değerlendirmeleri I/R grubu ile karşılaştırıldığında anlamlı düzeyde düşüktü (p=0.001). Sonuç: Apelinin oksidatif hasarı üzerinde olumlu etkisi olduğu görüldü, bu istatistiksel olarak anlamlı değildi. Bu yüzden insanlardan kullanılmadan önce, apelinin barsak iskemisinin başlangıç tedavisi ile ilgili bulgular üzerindeki rolü için daha büyük ölçekli hayvan çalışmalarına ihtiyaç vardır.

Anahtar Kelimeler

Apelin, mesenteric ischemia, reperfusion injury

The Effects of Apelin on Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Model

Öz

Kaynakça

• Diepenhorst GM, van Gulik TM, Hack CE. Complement-mediat- ed ischemia-reperfusion injury: lessons learned from animal and clinical studies. Ann Surg 2009;249:889-99. [CrossRef]
• Carden DL, Granger DN. Pathophysiology of ischaemia-reperfu- sion injury. J Pathol 2000;190:255-66. [CrossRef]
• Mallick IH, Yang W, Winslet MC, Seifalian AM. Ischemia-reper- fusion injury of the intestine and protective strategies against injury. Dig Dis Sci 2004;49:1359-77. [CrossRef]
• Petrescu BC, Gurzu B, Iancu RI, Indrei A, Dumitriu I, Chelaru L, et al. Apelin effects on lipopolysaccharide-increased pulmonary per- meability in rats. Rev Med Chir Soc Med Nat Iasi 2010;114:163-9.
• Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in ani- mal tissues by thiobarbutiric acid reaction. Anal Biochem 1979;95:351-8. [CrossRef]
• Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7. [CrossRef]
• Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemody- namic, and metabolic reappraisal. Arch Surg 1970;101:478-83. [CrossRef]
• Martinez JP, Hogan GJ. Mesenteric ischemia. Emerg Med Clin North Am 2004;22:909-28. [CrossRef]
• Chatterjee PK. Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review. Nau- nyn Schmiedebergs Arch Pharmacol 2007;376:1-43. [CrossRef]
• Anderson J, Fleming SD, Rehrig S, Tsokos GC, Basta M, Shea- Donohue T. Intravenous immunoglobulin attenuates mesenteric ischemia-reperfusion injury. Clin Immunol 2005;114:137-46. 16. Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and [CrossRef]
• Duggan M, Engelberts D, Jankov RP, Worrall JM, Qu R, Hare GM, et al. Hypocapnia attenuates mesenteric ischemia-reperfusion in- jury in a rat model. Can J Anaesth 2005;52:262-8. [CrossRef]
• Hassoun HT, Zou L, Moore FA, Kozar RA, Weisbrodt NW, Kone BC. Alpha-melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 2002;282:G1059-68.
• Petrat F, Rönn T, de Groot H. Protection by pyruvate infusion in a rat model of severe intestinal ischemia-reperfusion injury. J Surg Res 2011;167:e93-e101. [CrossRef]
• Sizlan A, Guven A, Uysal B, Yanarates O, Atim A, Oztas E, Cosar A, Korkmaz A. Proanthocyanidin protects intestine and remote organs against mesenteric ischemia/reperfusion injury. World J Surg 2009;33:1384-91. [CrossRef]
• Teke Z, Kabay B, Aytekin FO, Yenisey C, Demirkan NC, Sacar M, et al. Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats. Am J Surg 2007;194:255-62. [CrossRef] medicine. Pharmacol Ther 2005;107:198-211. [CrossRef]
• Kleinz MJ, Baxter GF. Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. Regul Pept 2008;146:271-7. [CrossRef]
• Simpkin JC, Yellon DM, Davidson SM, Lim SY, Wynne AM, Smith CC. Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemia-reperfusion injury. Basic Res Cardiol 2007;102:518-28. [CrossRef]
• Zeng XJ, Zhang LK, Wang HX, Lu LQ, Ma LQ, Tang CS. Apelin protects heart against ischemia/reperfusion injury in rat. Peptides 2009;30:1144-52. [CrossRef]
• Janssen M, Koster JF, Bos E, de Jong JW. Malondialdehyde and glutathione production in isolated perfused human and rat hearts. Circ Res 1993;73:681-8. [CrossRef]
• Turnage RH, Bagnasco J, Berger J, Guice KS, Oldham KT, Hin- shaw DB. Hepatocellular oxidant stress following intestinal isch- emia-reperfusion injury. J Surg Res 1991;51:467-71. [CrossRef]