Sıçanda stres ile uyarılan mide ülserinde simvastatin’in etkisi

Yıl 2016, Cilt: 29 Sayı: 1, 1 - 7, 04.03.2016

Elif Bahadır Elif Bahadır Muhammet Bulut Beyza Kabayuka Beyza Kabayuka Ece Söylem Şenkal Abdullah Avlaç Meral Yüksel Feriha Ercan İnci Alican , İnci Alican

https://doi.org/10.5472/MMJoa.2901.01

Öz

Amaç: Bu çalışmada sıçanlarda stres ile uyarılan mide ülserinde
simvastatin’in (SİM) olası koruyucu etkisini değerlendirmek
amaçlanmıştır.
Gereç ve Yöntem: Sprague-Dawley sıçanlarda (250-300
gr) soğuk-kısıtlama stres uygulaması ile mide ülseri oluşturuldu.
Stres öncesi 21 gün süreyle SİM (10 mg/kg/day; oral yolla) veya
fizyolojik tuzlu su (1 ml; oral yolla) uygulandı. Bir grup sıçan
21. günde SİM öncesi selektif olmayan nitrik oksit sentaz (NOS)
inhibitörü L-NAME (50 mg/kg; intraperitoneal) veya selektif
olmayan siklooksijenaz (COX) inhibitörü indometazin (İndo; 5
mg/kg; subkutan) verildi. Mideler makroskopik ve mikroskopik
olarak incelendi ve biyokimyasal analizler için saklandı.
Bulgular: Stres grubunda lezyonların şiddeti SİM ile azaldı
ancak L-NAME veya İndo ile anlamlı bir değişiklik göstermedi.
Stres mide miyeloperoksidaz aktivitesini kontrol düzeyine kıyasla
artırdı (p

Anahtar Kelimeler

Ülser, Nitrik oksit sentaz, Siklooksijenaz, Sıçan, Stres

Kaynakça

• 1. Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res 1995;31:9–27. doi:10.1016/1043-6618(95)80042-5
• 2. Simes J, Furberg CD, Braunwald E, Davis BR, Ford I, Tonkin A, Shepherd J. Effects of pravastatin on mortality on patients with and without coronary heart disease across a broad range of cholesterol levels. Eur Heart 2002;23:207–15.
• 3. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–9.
• 4. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Bere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279:1615–22. doi:10.1001/jama.279.20.1615.
• 5. Liao JK. Effect of statins on 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition beyond low-density lipoprotein cholesterol. Am J Cardiol 2005;96:24F–33F. doi:10.1016/j.amjcard.2005.06.009
• 6. Werner N, Nickeniq G, Laufs U. Pleiotropic effects of HMGCoA reductase inhibitors. Basic Res Cardiol 2002;97:105–16.
• 7. Trochu JN, Mital S, Zhang Xp, Xu X, Ochoa M, Liao JK, Recchia FA, Hintze TH. Preservation of NO production by statins in treatment of heart failure. Cardiovasc Res 2003;60:250-8. doi: http://dx.doi.org/10.1016/j. cardiores.2003.08.003.
• 8. Jiang JL, Jiang DJ, Tang YH, Li NS, Deng HW, Li YJ. Effect of simvastatin on endothelium-dependent vaso-relaxation and endogenous nitric oxide synthase inhibitor. Acta Pharmacol Sin 2004;25:893-901.
• 9. Dobrucki LE, Kalinowski L, Dobrucki IT, Malinski T. Statinstimulated nitric oxide release from endothelium. Med Sci Monit 2001;7:622-7.
• 10. Schror K, Lobel P, Steinhagen-Thiessen E. Simvastatin reduces platelet thromboxane formation and restores normal platelet sensitivity against prostacyclin in type IIa hypercholesterolemia. Eicanosoids 1989;2:39-45.
• 11. Scalia R, Gooszen ME, Jones SP, Hoffmeyer M, Rimmer DM 3rd, Trocha SD, Huang PL, Smith MB, Lefer AM, Lefer DJ. Simvastatin exerts both anti-inflammatory and cardioprotective effects in apoliprotein E-deficient mice. Circulation 2001;103:2598–603. doi: 10.1161/01. CIR.103.21.2598.
• 12. Pruefer D, Scalia R, Lefer AM. Simvastatin inhibits leukocytes– endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. Arterioscler Thromb Vasc Biol 1999;19:2894–900. doi: 10.1161/01.ATV.19.12.2894.
• 13. Ungureanu D, Filip C, Artenie A, Artenie R. Evaluation of simvastatin antioxidant effects. Rev Med Chir Soc Med Nat 2003;107:66–71.
• 14. Naidu BV, Woolley SM, Farivar AS, Thomas R, Fraga C, Mulligan MS. Simvastatin ameliorates injury in experimental model of lung ischemia-reperfusion. J Thorac Cardiovasc Surg 2003;126:482-9. doi:10.1016/S0022-5223(03)00699-8.
• 15. Inman SR, Davis NA, Olson KM, Lukaszek VA. Simvastatin attenuates renal ischemia/reperfusion injury in rats administered cyclosporine A. Am J Med Sci 2003;326:117- 21.
• 16. Rendig SV, Symons JD, Amterdam EA. Effects of statins on myocardial and coronary artery response to ischemiareperfusion. Can J Physiol Pharmacol 2003;81:1064-71. doi: 10.1139/y03-105.
• 17. Shabanzadeh AP, Shuaib A, Wang CX. Simvastatin reduced ischemic brain injury and perfusion deficits in an embolic model of stroke. Brain Res 2005;1042:1-5. doi:10.1016/j. brainres.2005.01.105
• 18. Tariq M, Khan HA, Elfaki I, Arshaduddin M, Al Moutaery M, Al Rayes H, Al Swailam R. Gastric antisecretory and antiulcer effects of simvastatin in rats. J Gastroenterol Hepatol 2007;22:2316–23. doi: 10.1111/j.1440-1746.2007.05021.x.
• 19. Heeba GH, Hassan MKA, Amin RS. Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. Eur J Pharmacol 2009;607:188–93. doi: 10.1016/j.ejphar.2009.02.008.
• 20. Yeomans N. The ulcer sleuths: the search fort he cause of peptic ulcers. J Gastroenterol Hepatol 2011;26:35-41. doi: 10.1111/j.1440-1746.2010.06537.x.
• 21. Senay EC, Levine RJ. Synergism between cold and restraint for rapid production of stress ulcer in rats. Proc Soc Exp Biol Med 1967;124:1221-3.
• 22. Jahovic N, Erkanli G, Işeri S, Arbak S, Alican I. Gastric protection by alpha-melanocyte-stimulating hormone against ethanol in rats: involvement of somatostatin. Life Sci 2007;80(11):1040-5. doi:10.1016/j.lfs.2006.11.036.
• 23. Aykac G, Uysal M, Yalcin AS, Kocak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione peroxidase and glutathione transferase in rat. Toxicology 1985:46:71–6.
• 24. Casini A, Ferrali M, Pompella AS, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene intoxicated mice. Am J Pathol 1986: 123:520–31.
• 25. Bradley PP, Preibat D, Christerser RD, Rothstein G. Measurement of cutaneous inflammation, estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982:78:206–9.
• 26. Haklar G, Ulukaya-Durakbasa C, Yuksel M, Dagli T, Yalcin AS. Oxygen radicals and nitric oxide in rat mesenteric ischemia-reperfusion: modulation by l-arginine and N-nitroL-arginine methyl ester. Clin Exp Pharmacol Physiol 1998;25:908–12. doi: 10.1111/j.1440-1681.1998.tb02342.x.
• 27. Kwiecien S, Brzozowski T, Konturek SJ. Effects of reactive oxygen species action on gastric mucosa in various models of mucosal injury. J Physiol Pharmacol 2002;53:39-50.
• 28. Brzozowski T, Konturek PC, Pajdo R, Ptak-Belowska A, Kwiecien S, Pawlik M, Drozdowicz D, Sliwowski Z, Brzozowski B, Konturek SJ, Pawlik WW. Physiological mediators in nonsteroidal anti-inflammatory drugs (NSAIDs)- induced impairment of gastric mucosal defense and adaptation. Focus on nitric oxide and lipoxins. J Physiol Pharmacol 2008;59:89-102.
• 29. Kwiecień S, Brzozowski T, Konturek PC, Pawlik MW, Pawlik WW, Kwiecień N, Konturek SJ. Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines. J Physiol Pharmacol 2004;55:337-55.
• 30. Kwiecień S, Brzozowski T, Konturek PC, Pawlik MW, Pawlik WW, Kwiecień N, Konturek SJ. The role of reactive oxygen species and capsaicin-sensitive sensory nerves in the pathomechanism of gastric ulcers induced by stress. J Physiol Pharmacol 2003;54:423-37.
• 31. Konturek SJ, Konturek PC. Role of nitric oxide in digestive system. Digestion 1995;56:1-13.
• 32. Sparrow CP, Burton CA, Hernandez M, Mundt S, Hassing H, Patel S, Rosa R, Hermanowski-Vosatka A, Wang PR, Zhang D, Peterson L, Detmers PA, Chao YS, Wright SD. Simvastation has anti-infallamtory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscler Thromb Vasc Biol 2001;21:115-21. doi: 10.1161/01.ATV.21.1.115.
• 33. Jahovic N, Gedik N, Ercan F, Şirvancı S, Yüksel M, Şener G, Alican İ. Effects of statins on experimental colitis in normocholesterolemic rats. Scand J Gastoenterol 2006;41:954- 62. doi: 10.1080/00365520600554444.
• 34. Bjarnason I, Scarpignato C, Takeuchi K, Rainsford KD. Determinants of the short-term gastric damage caused by NSAIDs in man. Aliment Pharmacol Ther 2007;26(1):95-106. doi: 10.1111/j.1365-2036.2007.03348.x.
• 35. Lopez-Belmonte J,Whittle BJ,Moncada S. The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa. Br J Pharmacol 1993;108(1):73-8. doi: 10.1111/j.1476-5381.1993.tb13442.x.
• 36. Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal antiinflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr 2011;48:107-11. doi: http://doi. org/10.3164/jcbn.10-79.
• 37. Konturek SJ, Piastucki I, Brzozowski T, Radecki T, Dembińska-Kieć A, Zmuda A, Gryglewski R. Role of prostaglandins in the formation of aspirin-induced gastric ulcers. Gastroenterology 1981;80:4-9.