Abstract
Ischemia-reperfusion damage causes high morbidity and mortality for patients who have clinical conditions such as myocardial infarction, organ transplantations, cerebrovascular infarction, cardiopulmonary resuscitation, thrombolytic therapy and hemorrhagic shock. Ischemic tissue damage starting with decreasing blood supply and oxygen deficiency in affected tissues increases through reoxygenation when reperfusion provided. Decreasing mitochondrial ATP production causes shift from aerobic to anaerobic intracellular metabolism and leads to acidosis. Decelerating of ATP dependent Na-K pumps leads to increased intracellular hydrogen load. This increase in hydrogen ions is balanced with increased intracellular calcium levels via Na-Ca pumps. Increased calcium ions also activate many cytosolic proteases. Tissue reoxygenation with reperfusion accelerates several critical biochemical pathways for the production of reactive oxygen species (ROS) such as hydroxyl radicals (OH•), superoxide radicals (O2•-) and hydrogen peroxides H2O2 and reactive nitrogen species (RNS) such as peroxynitrides (ONOO-). However, increased reactive radicals can lead to collection of inflammatory cells to the inflammatory region. Cytokines released through the interaction between inflammatory (especially polymorphonuclear leukocytes) and endothelial cells cause expanding of damage due to reperfusion. Xanthine oxidase, nitric oxide synthase, NADPH oxidase, which is responsible for respiratory burst in phagocytes, and electron transport chain in mitochondria are the main mechanisms responsible for the production of ROS and RNS. These free radicals attack important macromolecules such as lipid structures of cell membranes, intracellular proteins and genetic material and can cause cell damage and death. Since ischemiareperfusion injury is a quite complex process, the relationship between ischemia-reperfusion and oxidative stress mainly discussed in this review
References
- Douzinas EE, Livaditi O, Tasoulis MK, Prigouris P, Bakos D, Goutas N, et al. Nitrosative and oxidative stresses contribute to post-ischemic liver injury following severe hemorrhagic shock:the role of hypoxemic resuscitation. PLoS ONE 2012;7:3.
- Arkadopoulos N, Defterevos G, Nastos C, Papalois A, Kalimeris K, Papoutsidakis N, et al. Development of a porcine model of post-hepatectomy liver failure. J Surg Res 2011;170:233-42.
- Jaeschke H. Molecular mechanisms of hepaticischemia reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:15-26.
- Homer-Vanniasinkam S, Crinnionand JN, Gough MJ. Post-ischaemic organ dysfunction: a review. Eur J Vasc Endovasc Surg 1997;14:195-203.
- Gupta RK, Patel AK, Shah N, Chaudhary AK, Jha UK, Yadav UC et al. Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev 2014;15:4405-9.
- Dokuyucu R, Karateke A, Gokce H, Kurt RK, Ozcan O, Ozturk S, et al. Antioxidant effects of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol 2014;183:23-7.
- Granger DN, Rutili G, McCord JM. Role of superoxide radicals in intestinal ischemia. Gastroenterology 1981;81:22-29.
- Baines CP. The mitochondrial permeability transition pore and ischemia-reperfusion injury. Basic Res Cardiol 2009;104:181–8.
- Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning and translational aspects of protective measures. Am J Physiol 2011;301:1723–41.
- De Martino GN. Calcium-dependent proteolytic activity in rat liver: identification of two proteases with different calcium requirements. Arch Biochem Biophys 1981;211:253-7.
- Schaffer SW, Roy RS, and McCord JM. Possible role for calmodulin in calcium paradox-induced heart failure. Eur Heart J 1983;4:81-7.
- Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12:1161-208.
- Esterbauer H, Schaur RJ, Zollner H. Chemistry andbiochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11:81-128.
- Catalá A. An overview of lipid peroxidation with emphasis in outer segments of photoreceptors and the chemiluminescence assay. Int J Biochem Cell Biol 2006;38:1482-95.
- Solaini G, Harris DA. Biochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion. Biochem J 2005;390:377–94.
- Di Lisa F, Kaludercic N, Carpi A, Menabó R, Giorgio M. Mitochondrial pathways for ROS formation and myocardial injury: the relevance of p66 (Shc) and monoamine oxidase. Basic Res Cardiol 2009;104:131–9.
- Kvietys PR, Granger DN. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med 2012;52:556–92.
- Serracino-Inglott F, Habib NA, and Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg 2001;181:160–6.
- Schmid-Schoenbein GW and Engler RL. Granulocytes as active participants in acute myocardial ischemia and infarction. Am J Cardiovasc Pathol 1987;1:15–30.
- Hansson RO, Jonsson O, Lundstam S, Petterson S, Schersten T, Waldenström J. Effects of free radical scavengers on renal circulation after ischemia in the rabbit. Clin Sci 1983;65:605-10. de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. American Journal of Respiratory and Critical Care Medicine 2003;167, 490-511.
- Pan J, Konstas AA, Bateman B, Ortolano GA, John Pile-Spellman J. Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology 2007;49: 93–102.
- Dworakowski R, Walker S, Momin A, Desai J, El-Gamel A, Wendler O, et al. Reduced nicotin amide adenine dinucleotide phosphate oxidase-derived superoxide and vascular endothelial dysfunction in human heart failure. J Am Coll Cardiol 2008;51:1349–56.
- Rodriguez SF, Granger DN. Role of blood cells in ischemia-reperfusion-induced endothelial barrier failure. Cardiovasc Res 2010;87:291–9.
- Parks DA, Granger DN. Xanthineoxidase: biochemistry distribution and physiology. Acta Physiol Scand 1986;548:87–99.
- Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012;298:229-317.
- Phillips L, Toledo AH, Lopez-Neblina F, Anaya-Prado R, Toledo-Pereyra LH. Nitric oxide mechanism of protection in ischemia and reperfusion injury. J Invest Surg 2009;22:46-55.
- Szocs K. Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. Gen Physiol Biophys 2004;23:265-95.
- Hein TW, Zhang C, Wang W, Chang CI, Thengchaisri N, Kuo L. Ischemia-reperfusion selectively impairs nitric oxide-mediated dilation in coronary arterioles: counteracting role of arginase. FASEB J 2003;17:2328–30.
- Esme H, Fidan H, Koken T, Solak O. Effect of lung ischemia-reperfusion on oxidative stres parameters of remote tissues. Eur J Cardiothorac Surg 2006;29:294–8.
- Vaghasiya JD, Sheth NR, Bhalodia YS, Jivani NP. Exaggerated liver injury produced by renal ischemia reperfusion in diabetes: effect of exenatide. Saudi J Gastroenterol 2010;16:174–180.
- Hirsch J, Niemann CU, Hansen KC, Choi SJN, Su X, Frank JA, et al. Alterations in the proteome of pulmonary alveolar type II cells in the rat after hepatic ishchemia-reperfusion. Crit Care Med 2008;36:1846–54.
- Vega VL, Mardones L, Maldonado M, Nicovani S, Manriquez V, Roa J, et al. Xanthine oxidase released from reperfused hindlimbs mediate kupffer cell activation, neutrophil sequestration, and hepatic oxidative stress in rats subjected to tourniquet shock. Shock 2000;14:565–71.
- He GZ, Dong LG, Chen XF, Zhou KG, Shu H. Lymphduct ligation during ischemia/reperfusion prevents pulmonary dysfunction in a rat model with omega-3 polyunsaturated fatty acid and glutamine. Nutrition 2011;27:604–14.
- Carden DL, Granger DN. Pathophysiology of ischemia-reperfusion injury. J Pathol 2000;190:255–66.
Abstract
İskemi-reperfüzyon hasarı; miyokard infarktüsü, serebrovasküler infarkt, organ transplantasyonları, kardiyopulmoner resusitasyon, trombolitik tedavi ve hemorajik şok gibi birçok klinik durumda halen hastalar için yüksek morbidite ve mortalite nedenidir. Dokuya giden kan akımının azalması ve oksijen yetersizliği ile başlayan iskemik doku hasarı, reperfüzyon sağlandığında hasarlanmış dokuların yeniden oksijenasyonu ile artarak devam eder. Hücrelerdeki mitokondriyel ATP üretiminin azalması hücre içi metabolizmanın anaerobik yöne kaymasına ve hücre içi asidoza sebep olur. ATP bağımlı Na-K iyon pompalarının yavaşlaması, hücre içi hidrojen artışına yol açar. Artmış hidrojen yükünü dengelemek için ATP bağımlı olmayan Na-Ca pompası intraselüler kalsiyum miktarını artırır. Artmış kalsiyum yükü ise birçok sitozolik proteazı aktive eder. Hücre içi proteaz aktivasyonu ve reperfüzyonla dokuların yeniden oksijenasyonu ise sonuçta hidroksil radikali (OH•), süperoksit radikali (O2•−) ve hidrojen peroksit H2O2 gibi reaktif oksijen türleri (ROS) ile peroksinitrit (ONOO-) gibi reaktif nitrojen türlerinin (RNS) üretimine yol açan kritik biyokimyasal yolakları hızlandırır. Ayrıca artmış serbest radikallerin neden olduğu inflamasyon, bölgeye inflamatuvar hücrelerin toplanmasını tetikler. Endotelyal hücrelerle başta polimorf çekirdekli lökositler olmak üzere inflamatuvar hücreler arasındaki etkileşimler, birçok sitokinin salınmasına ve iskeminin yol açtığı hasarın reperfüzyonla genişlemesine yol açar. Ksantin oksidaz, nitrik oksit sentaz, mitokondrilerde bulunan elektron transport zinciri ve fagositlerdeki solunumsal patlamadan sorumlu NADPH oksidaz, ROS ve RNS üretiminden sorumlu başlıca mekanizmalardır. Sonuçta oluşan serbest radikaller hücre membranlarındaki lipit yapılar, hücre içi yapısal ve fonksiyonel proteinler ve genetik materyal gibi önemli makromoleküllere zarar vererek hücre hasarı veya ölümüne yol açarlar. İskemi-reperfüzyonda hasar oluşumu oldukça kompleks bir süreç olup, bu derlemede başlıca oksidatif stres ile ilişkisi ele alınmıştır.
References
- Douzinas EE, Livaditi O, Tasoulis MK, Prigouris P, Bakos D, Goutas N, et al. Nitrosative and oxidative stresses contribute to post-ischemic liver injury following severe hemorrhagic shock:the role of hypoxemic resuscitation. PLoS ONE 2012;7:3.
- Arkadopoulos N, Defterevos G, Nastos C, Papalois A, Kalimeris K, Papoutsidakis N, et al. Development of a porcine model of post-hepatectomy liver failure. J Surg Res 2011;170:233-42.
- Jaeschke H. Molecular mechanisms of hepaticischemia reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:15-26.
- Homer-Vanniasinkam S, Crinnionand JN, Gough MJ. Post-ischaemic organ dysfunction: a review. Eur J Vasc Endovasc Surg 1997;14:195-203.
- Gupta RK, Patel AK, Shah N, Chaudhary AK, Jha UK, Yadav UC et al. Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev 2014;15:4405-9.
- Dokuyucu R, Karateke A, Gokce H, Kurt RK, Ozcan O, Ozturk S, et al. Antioxidant effects of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol 2014;183:23-7.
- Granger DN, Rutili G, McCord JM. Role of superoxide radicals in intestinal ischemia. Gastroenterology 1981;81:22-29.
- Baines CP. The mitochondrial permeability transition pore and ischemia-reperfusion injury. Basic Res Cardiol 2009;104:181–8.
- Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning and translational aspects of protective measures. Am J Physiol 2011;301:1723–41.
- De Martino GN. Calcium-dependent proteolytic activity in rat liver: identification of two proteases with different calcium requirements. Arch Biochem Biophys 1981;211:253-7.
- Schaffer SW, Roy RS, and McCord JM. Possible role for calmodulin in calcium paradox-induced heart failure. Eur Heart J 1983;4:81-7.
- Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12:1161-208.
- Esterbauer H, Schaur RJ, Zollner H. Chemistry andbiochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11:81-128.
- Catalá A. An overview of lipid peroxidation with emphasis in outer segments of photoreceptors and the chemiluminescence assay. Int J Biochem Cell Biol 2006;38:1482-95.
- Solaini G, Harris DA. Biochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion. Biochem J 2005;390:377–94.
- Di Lisa F, Kaludercic N, Carpi A, Menabó R, Giorgio M. Mitochondrial pathways for ROS formation and myocardial injury: the relevance of p66 (Shc) and monoamine oxidase. Basic Res Cardiol 2009;104:131–9.
- Kvietys PR, Granger DN. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med 2012;52:556–92.
- Serracino-Inglott F, Habib NA, and Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg 2001;181:160–6.
- Schmid-Schoenbein GW and Engler RL. Granulocytes as active participants in acute myocardial ischemia and infarction. Am J Cardiovasc Pathol 1987;1:15–30.
- Hansson RO, Jonsson O, Lundstam S, Petterson S, Schersten T, Waldenström J. Effects of free radical scavengers on renal circulation after ischemia in the rabbit. Clin Sci 1983;65:605-10. de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. American Journal of Respiratory and Critical Care Medicine 2003;167, 490-511.
- Pan J, Konstas AA, Bateman B, Ortolano GA, John Pile-Spellman J. Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology 2007;49: 93–102.
- Dworakowski R, Walker S, Momin A, Desai J, El-Gamel A, Wendler O, et al. Reduced nicotin amide adenine dinucleotide phosphate oxidase-derived superoxide and vascular endothelial dysfunction in human heart failure. J Am Coll Cardiol 2008;51:1349–56.
- Rodriguez SF, Granger DN. Role of blood cells in ischemia-reperfusion-induced endothelial barrier failure. Cardiovasc Res 2010;87:291–9.
- Parks DA, Granger DN. Xanthineoxidase: biochemistry distribution and physiology. Acta Physiol Scand 1986;548:87–99.
- Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012;298:229-317.
- Phillips L, Toledo AH, Lopez-Neblina F, Anaya-Prado R, Toledo-Pereyra LH. Nitric oxide mechanism of protection in ischemia and reperfusion injury. J Invest Surg 2009;22:46-55.
- Szocs K. Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. Gen Physiol Biophys 2004;23:265-95.
- Hein TW, Zhang C, Wang W, Chang CI, Thengchaisri N, Kuo L. Ischemia-reperfusion selectively impairs nitric oxide-mediated dilation in coronary arterioles: counteracting role of arginase. FASEB J 2003;17:2328–30.
- Esme H, Fidan H, Koken T, Solak O. Effect of lung ischemia-reperfusion on oxidative stres parameters of remote tissues. Eur J Cardiothorac Surg 2006;29:294–8.
- Vaghasiya JD, Sheth NR, Bhalodia YS, Jivani NP. Exaggerated liver injury produced by renal ischemia reperfusion in diabetes: effect of exenatide. Saudi J Gastroenterol 2010;16:174–180.
- Hirsch J, Niemann CU, Hansen KC, Choi SJN, Su X, Frank JA, et al. Alterations in the proteome of pulmonary alveolar type II cells in the rat after hepatic ishchemia-reperfusion. Crit Care Med 2008;36:1846–54.
- Vega VL, Mardones L, Maldonado M, Nicovani S, Manriquez V, Roa J, et al. Xanthine oxidase released from reperfused hindlimbs mediate kupffer cell activation, neutrophil sequestration, and hepatic oxidative stress in rats subjected to tourniquet shock. Shock 2000;14:565–71.
- He GZ, Dong LG, Chen XF, Zhou KG, Shu H. Lymphduct ligation during ischemia/reperfusion prevents pulmonary dysfunction in a rat model with omega-3 polyunsaturated fatty acid and glutamine. Nutrition 2011;27:604–14.
- Carden DL, Granger DN. Pathophysiology of ischemia-reperfusion injury. J Pathol 2000;190:255–66.
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Review |
| Authors | |
| Publication Date | September 30, 2015 |
| Submission Date | August 17, 2015 |
| Published in Issue | Year 2015 Volume: 6 Issue: 23 |
