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ABDOMİNAL AORTA İSKEMİ- REPERFÜZYONUNA BAĞLI GELİŞEN AKCİĞER HASARINDA KARNOZİNİN ETKİSİ

Year 2010, Volume: 11 Issue: 3, 41 - 47, 16.12.2010

Abstract

AMAÇ:Aortanın geçici olarak klemplenmesini gerektiren cerrahi girişimlerden sonra, alt ekstremitelerdeiskemi/reperfüzyon (İR) hasarı ve akciğerlerde uzak organ hasarı oluşabilir. İR hasarında nötrofillerinaktivasyonunun önemli bir rol oynadığı bilinmektedir. Amacımız rat modelinde abdominal aortanınklemplenmesini takiben oluşan akciğer iskemi reperfüzyon hasarında karnozinin etkisini araştırmaktır.GEREÇ ve YÖNTEM:Yirmidört adet Sprague-Dawley cinsi rat, rasgele ve eşit sayıda (n=8) olmak üzere üçgruba ayrıldı. Grup 1 deki ratlarda batın açıldı ve abdominal aortları eksplore edildikten sonra hiçbir girişimyapılmadan tekrar kapatıldı. Grup 2'de abdominal aortaya klemp konuldu. 30 dakika iskemi süresinin sonundaklemp kaldırıldı ve 60 dakika reperfüzyon gerçekleştirildi. 2. grupdaki işlemin aynısı karnozin verilen 3. gruba dauygulandı ve karnozin intraperitoneal yolla klemp kaldırılmadan 10 dakika önce, 250 mg/kg olarak verildi. Tümgruplardaki ratlar reperfüzyon süresinin tamamlanmasıyla sakrifiye edildi. Histolojik inceleme ve biyokimyasalanalizler için akciğer doku örnekleri alındı.BULGULAR:Akciğer dokusunda Grup 2'ye ait malonil dialdehit, süperoksit dismutaz, myeloperoksidaz,okside glutatyon ve total glutatyon değerleri kontrol grubundaki değerlere göre anlamlı derecede yüksek bulundu(p<0,05). Grup 3'e ait malonil dialdehit ve okside glutatyon değerleri, aortik iskemi reperfüzyon grubundakideğerlere göre anlamlı derecede düşük bulundu (p<0,05). İmmünohistokimyasal değerlendirmede iNOS içinimmünreaktivitenin grup 1'de olmadığı, grup 2'de şiddetli düzeyde olduğu grup 3'de ise hafif düzeyde olduğugörüldü.SONUÇ:Karnozinin, abdominal aortanın geçici iskemi reperfüzyon hasarına bağlı olarak akciğerlerde oluşanpatolojik değişikleri önlemede yararlı etkileri bulunmaktadır

References

  • 1. Car den DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000;190:255- 66.
  • 2. Yassin MM, Harkin DW, Barros AA, Halliday MI, Rowlands BJ. Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction.World J Surg 2002;26:115-21.
  • 3. Goldman G, Welbourn R, Klausner JM, Kobzik L, Valeri CR, Shepro D. Mast cells and leukotrienes mediate neutrophil sequestration and lung edema after remote ischemia in rodents. Surgery 1992;112:578-86.
  • 4. Nakamura T, Vollmar B, Winning J, Ueda M, Menger MD, Schafers HJ. Heparin and the nonanticoagulant Nacetyl heparin attenuate capillary no-reflow after normothermic ischemia of the lung. Ann Thorac Surg 2001;72(4):1183-8.
  • 5. Pepine CJ. The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther 1991;13(1):2-21.
  • 6. McGuire, Liu P, Jaeschke H. Neutrophil-included lung damage after hepatic ischemia and endotoxemia. Free Radic Biol Med 1996;20:189-97.
  • 7. Punch J, Rees R, Cashmer B. Acute lung injury following reperfusion ischemia in the hind limbs of rats. J Trauma 1991;31:760-5.
  • 8. Stvolinsky SL, Dobrota D. Anti-ischemic activity of carnosine. Biochemistry 2000;65:849- 55.
  • 9. Boldyrev A, Severin SE. The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance. Adv Enzyme Regul 1990;30:175-94.
  • 10. Stvolinsky SL, Kukley ML, Dobrota D, Matejovicova M, Tkac I, Boldyrev AA. Carnosine: an endogenous neuroprotector in the ischemic brain. Cell Mol Neurobiol 1999;19(1):45-56.
  • 11. Fujii T, Takaoka M, Muraoka T, Kurata H, Tsuruoka N, Ono H, Kiso Y, Tanaka T, Matsumura Y. Preventive effect of L-carnosine on ischemia/reperfusion-induced acute renal failure in rats. Eur J Pharmacol 2003;474(2-3):261-7.
  • 12. Witt EH, Reznick AZ, Viguie CA, Starke Reed P, Packer L. Exercise, oxidative damage and effects of antioxidant manipulation. J Nutr 1992;122:766-73.
  • 13. Pick E, Keisari V. Superoxide anion and H O production by chemically elicited peritoneal macrophage induced by multiple nonphagocytic stimuli. Cell Immunol 1981;59:301-18.
  • 14. Kantha SS, Wada S, Tanaka H, Takeuchi M, Watabe S, Ochi H. Carnosine sustains the retention of cell morphology in continuous fibroblast culture subjected to nutritional insult. Biochem Biophys Res Commun 1996;223(2):278-82.
  • 15. Suzuki K, Ota H, Sasagawa S. Assay method for myeloperoxidase in human polymorphonuclear leukocytes.Anal Biochem 1983;132:345-52.
  • 16. Pontoppidan H, Geffın B, Lowenstein E. Acute respiratory failure in the adult. N Engl J Med 1972;287:690-806.
  • 17. Dantzker DR, Scharf SM. Cardiopulmonary critical care. 3 Edition: WB Saunders, Philadelphia, 1998:41- 2.
  • 18. Mueller HW, Nollert MU, Eskin SG. Synthesis of stuctural analog of platelet activating factor, by vascular endothelial cells. Biochem Biophys Res Common 1991;176:1557-64.
  • 19. Köksoy C, Kuzu MA, Ergün H, Gürhan I. Role of tumor necrosis factor in lung injury caused by intestinal ischemia-reperfusion. Br J Surg 2001;88:464-8.
  • 20. Halliwell B. Superoxide, iron, vascular endothelium and injury. Free Radic Res Common 1989;5:315-18
  • 21. Boldyrev A, Bulygina E, Leinsoo T, Petrushanko I, Tsubone S, Abe H. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds. Comp Biochem Physiol B Biochem Mol Biol 2004;137(1):81-8 .
  • 22. Hipkiss AR. Carnosine, a protective, anti-ageing peptide? Int J Biochem Cell Biol 1998;30:863-8.
  • 23. Lee JW, Miyawaki H, Bobst EV, Hester JD. Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine. J Mol Cell Cardiol 1999;31:113-21.
  • 24. Choi SY, Kwon HY, Kwon OB, Kang JH. Hydrogen peroxide-mediated Cu, Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine. Biochim Biophys Acta 1999;1472(3): 651-7.
  • 25. Hipkiss AR, Preston JE, Himswoth HY, Worthington VC, Abboth NJ. Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells. Neurosci Lett 1997;238(3):135- 8.
  • 26. Sakamaki F, Hoffmann H, Muller C, Dienemann H, Messmer K, Schildberg FW. Reduced lipid peroxidation and ischemia reperfusion injury after lung transplantation using low-potassium dextran solution for lung preservation. Am J Respir Crit Care Med 1997;156(4):1073-81.
  • 27. Uysal A, Akar İ, Özsin KK, Rahman A, Üstündag B, Özercan Hİ. Alt ekstremite iskemi reperfüzyonunun yol açtıgı akciger hasarında melatoninin koruyucu etkinligi. Türk Gögüs Kalp Damar Cerrahisi Dergisi 2006;4:308-14.
  • 28. Okutan H, Savas Ç, Delibas N. The antioxidant effect of melatonin in lung injury after aortic occlusionreperfusion. Interact Cardiovasc Thorac Surg 2004;3:519-22.
  • 29. Baltalarlı A, Ozcan V, Bir F, Aybek H, Sacar M, Onem G, Goksin I, Demir S, Teke Z. Ascorbic acid (vitamin C) and iloprost attenuate the lung injury caused by ischemia/reperfusion of the lower extremities of rats. Ann Vasc Surg 2006;20(1):49-55.
  • 30. Clark IA. Tissue damage caused by free oxygen radicals. Pathology 1986;18:181-6.
  • 31. Toyokuni S. Reactive oxygen species-induced molecular damage and its application in pathology. Pathol Int 1999;49:91-102.
  • 32. Dimakakos PB, Kotsis T, Kondi-Pafiti A, Katsenis K, Doufas A, Chondros K, Kouskouni E. Oxygen free radicals in abdominal aortic surgery. An experimantal study. J Cardiovasc Surg 2002;43(1):77-82.
  • 33. İlhan A, Koltuksuz U, Özen S, Uz E, Çıralık H, Akyol O. The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg 1999;16(4):458-63.
  • 34. Ege E, Ilhan A, Gurel A, Akyol O, Ozen S. Erdosteine ameliorates neurological outcome and oxidative stress due to ischemia/reperfusion injury in rabbit spinal cord. Eur J Vasc Endovasc Surg 2004;28(4):379-86.
  • 35. Tassiopoulos A, Carlin RE, Gao Y. Role of nitric oxide and tumor necrosis factor on lung injury caused by ischemia/reperfusion of the lower extremities. J Vasc Surg 1997;26:647-56.
  • 36. Vural KM, Öz MC. Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemiareperfusion. Eur J Cardiothorac Surg 2000;18:348-52.

The Effect of Carnosine on Lung Injury Induced by Abdominal Aortic Ischemia-Reperfusion

Year 2010, Volume: 11 Issue: 3, 41 - 47, 16.12.2010

Abstract

OBJECTIVE: The purpose of this study is to examine the effect of carnosine on ischemia reperfusion injury in lungs occuring after occlusion reperfusion of infrarenal abdominal aorta in rats. MATERIALS and METHODS: Twentyfour Sprague-Dawley rats were randomly divided into 3 groups (n=8). Sham laparotomy (control) group (Group 1) underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. In aortic ischemia reperfusion groups (group 2 and 3), after laparotomy and exteriorization of the infrarenal abdominal aorta, aorta was occluded for 30 min ischemia and then the clamp was removed for 60 min reperfusion. In group 3; 250mg/kg carnosine, were given intraperitoneally 10 min before declamping aorta. The lung tissue specimens were taken for biochemical analysis and immunohistochemical examination. RESULTS: In lung specimens, malonil dialdehyde, oxidized glutathione and total glutathione levels, and superoxide dismutase and myeloperoxidase activities were significantly higher in the aortic ischemia reperfusion (group 2) than the sham laparotomy (control) group (p<0.05). Levels of malonil dialdehyde and oxidized glutathione were significantly lower in the aortic ischemia reperfusion and carnosine group (group 3) than the aortic ischemia reperfusion one (p<0.05). While iNOS immunoreactivities were severe in group 2 and mild in group 3, they were not observed in group 1. CONCLUSION: Carnosine was beneficial in prevention of lung injury after abdominal aortic occlusionreperfusion injury.

References

  • 1. Car den DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000;190:255- 66.
  • 2. Yassin MM, Harkin DW, Barros AA, Halliday MI, Rowlands BJ. Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction.World J Surg 2002;26:115-21.
  • 3. Goldman G, Welbourn R, Klausner JM, Kobzik L, Valeri CR, Shepro D. Mast cells and leukotrienes mediate neutrophil sequestration and lung edema after remote ischemia in rodents. Surgery 1992;112:578-86.
  • 4. Nakamura T, Vollmar B, Winning J, Ueda M, Menger MD, Schafers HJ. Heparin and the nonanticoagulant Nacetyl heparin attenuate capillary no-reflow after normothermic ischemia of the lung. Ann Thorac Surg 2001;72(4):1183-8.
  • 5. Pepine CJ. The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther 1991;13(1):2-21.
  • 6. McGuire, Liu P, Jaeschke H. Neutrophil-included lung damage after hepatic ischemia and endotoxemia. Free Radic Biol Med 1996;20:189-97.
  • 7. Punch J, Rees R, Cashmer B. Acute lung injury following reperfusion ischemia in the hind limbs of rats. J Trauma 1991;31:760-5.
  • 8. Stvolinsky SL, Dobrota D. Anti-ischemic activity of carnosine. Biochemistry 2000;65:849- 55.
  • 9. Boldyrev A, Severin SE. The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance. Adv Enzyme Regul 1990;30:175-94.
  • 10. Stvolinsky SL, Kukley ML, Dobrota D, Matejovicova M, Tkac I, Boldyrev AA. Carnosine: an endogenous neuroprotector in the ischemic brain. Cell Mol Neurobiol 1999;19(1):45-56.
  • 11. Fujii T, Takaoka M, Muraoka T, Kurata H, Tsuruoka N, Ono H, Kiso Y, Tanaka T, Matsumura Y. Preventive effect of L-carnosine on ischemia/reperfusion-induced acute renal failure in rats. Eur J Pharmacol 2003;474(2-3):261-7.
  • 12. Witt EH, Reznick AZ, Viguie CA, Starke Reed P, Packer L. Exercise, oxidative damage and effects of antioxidant manipulation. J Nutr 1992;122:766-73.
  • 13. Pick E, Keisari V. Superoxide anion and H O production by chemically elicited peritoneal macrophage induced by multiple nonphagocytic stimuli. Cell Immunol 1981;59:301-18.
  • 14. Kantha SS, Wada S, Tanaka H, Takeuchi M, Watabe S, Ochi H. Carnosine sustains the retention of cell morphology in continuous fibroblast culture subjected to nutritional insult. Biochem Biophys Res Commun 1996;223(2):278-82.
  • 15. Suzuki K, Ota H, Sasagawa S. Assay method for myeloperoxidase in human polymorphonuclear leukocytes.Anal Biochem 1983;132:345-52.
  • 16. Pontoppidan H, Geffın B, Lowenstein E. Acute respiratory failure in the adult. N Engl J Med 1972;287:690-806.
  • 17. Dantzker DR, Scharf SM. Cardiopulmonary critical care. 3 Edition: WB Saunders, Philadelphia, 1998:41- 2.
  • 18. Mueller HW, Nollert MU, Eskin SG. Synthesis of stuctural analog of platelet activating factor, by vascular endothelial cells. Biochem Biophys Res Common 1991;176:1557-64.
  • 19. Köksoy C, Kuzu MA, Ergün H, Gürhan I. Role of tumor necrosis factor in lung injury caused by intestinal ischemia-reperfusion. Br J Surg 2001;88:464-8.
  • 20. Halliwell B. Superoxide, iron, vascular endothelium and injury. Free Radic Res Common 1989;5:315-18
  • 21. Boldyrev A, Bulygina E, Leinsoo T, Petrushanko I, Tsubone S, Abe H. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds. Comp Biochem Physiol B Biochem Mol Biol 2004;137(1):81-8 .
  • 22. Hipkiss AR. Carnosine, a protective, anti-ageing peptide? Int J Biochem Cell Biol 1998;30:863-8.
  • 23. Lee JW, Miyawaki H, Bobst EV, Hester JD. Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine. J Mol Cell Cardiol 1999;31:113-21.
  • 24. Choi SY, Kwon HY, Kwon OB, Kang JH. Hydrogen peroxide-mediated Cu, Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine. Biochim Biophys Acta 1999;1472(3): 651-7.
  • 25. Hipkiss AR, Preston JE, Himswoth HY, Worthington VC, Abboth NJ. Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells. Neurosci Lett 1997;238(3):135- 8.
  • 26. Sakamaki F, Hoffmann H, Muller C, Dienemann H, Messmer K, Schildberg FW. Reduced lipid peroxidation and ischemia reperfusion injury after lung transplantation using low-potassium dextran solution for lung preservation. Am J Respir Crit Care Med 1997;156(4):1073-81.
  • 27. Uysal A, Akar İ, Özsin KK, Rahman A, Üstündag B, Özercan Hİ. Alt ekstremite iskemi reperfüzyonunun yol açtıgı akciger hasarında melatoninin koruyucu etkinligi. Türk Gögüs Kalp Damar Cerrahisi Dergisi 2006;4:308-14.
  • 28. Okutan H, Savas Ç, Delibas N. The antioxidant effect of melatonin in lung injury after aortic occlusionreperfusion. Interact Cardiovasc Thorac Surg 2004;3:519-22.
  • 29. Baltalarlı A, Ozcan V, Bir F, Aybek H, Sacar M, Onem G, Goksin I, Demir S, Teke Z. Ascorbic acid (vitamin C) and iloprost attenuate the lung injury caused by ischemia/reperfusion of the lower extremities of rats. Ann Vasc Surg 2006;20(1):49-55.
  • 30. Clark IA. Tissue damage caused by free oxygen radicals. Pathology 1986;18:181-6.
  • 31. Toyokuni S. Reactive oxygen species-induced molecular damage and its application in pathology. Pathol Int 1999;49:91-102.
  • 32. Dimakakos PB, Kotsis T, Kondi-Pafiti A, Katsenis K, Doufas A, Chondros K, Kouskouni E. Oxygen free radicals in abdominal aortic surgery. An experimantal study. J Cardiovasc Surg 2002;43(1):77-82.
  • 33. İlhan A, Koltuksuz U, Özen S, Uz E, Çıralık H, Akyol O. The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg 1999;16(4):458-63.
  • 34. Ege E, Ilhan A, Gurel A, Akyol O, Ozen S. Erdosteine ameliorates neurological outcome and oxidative stress due to ischemia/reperfusion injury in rabbit spinal cord. Eur J Vasc Endovasc Surg 2004;28(4):379-86.
  • 35. Tassiopoulos A, Carlin RE, Gao Y. Role of nitric oxide and tumor necrosis factor on lung injury caused by ischemia/reperfusion of the lower extremities. J Vasc Surg 1997;26:647-56.
  • 36. Vural KM, Öz MC. Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemiareperfusion. Eur J Cardiothorac Surg 2000;18:348-52.
There are 36 citations in total.

Details

Other ID JA34TY55TN
Journal Section Research Article
Authors

Bilge Alaçam This is me

Rauf Onur Ek This is me

Yüksel Yıldız This is me

Mukadder Serter This is me

Nezihe Tülün Boylu This is me

Sadun Temoçın This is me

Publication Date December 16, 2010
Published in Issue Year 2010 Volume: 11 Issue: 3

Cite

EndNote Alaçam B, Ek RO, Yıldız Y, Serter M, Boylu NT, Temoçın S (December 1, 2010) The Effect of Carnosine on Lung Injury Induced by Abdominal Aortic Ischemia-Reperfusion. Meandros Medical And Dental Journal 11 3 41–47.