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Effect of montelukast on hepatic and renal ischemia/reperfusion injury

Yıl 2017, Cilt 8, Sayı 2, 43 - 51, 18.06.2017
https://doi.org/10.18663/tjcl.304530

Öz

Aim: The thoracoabdominal aortic aneurysm surgery may cause splanchnic ischemia and may result in severe postoperative complications caused by liver and/or kidney injury. This study investigated the effect of temporary occlusion of the aorta on the development of I/R injury of liver and kidney and the protective effect of montelukast, a selective reverse CysLT1 receptor antagosit.

 Material and Methods: Twenty-one male Sprague-Dawley rats were randomly assigned to three groups (n=7 per group) as G1 (no aortic occlusion and montelukast administration), G2 (45 min. aortic occlusion; no montelukast administration) and G3 (45 min. aortic occlusion, 10 mg/kg montelukast administration). At the 48th hour of reperfusion, kidney and liver samples were dissected for histopathological evaluation and immunohistochemical staining for HSP70, interleukin-6 and myeloperoxidase (MPO).

 Results: Tissue samples taken from the kidney showed significant intergroup differences in terms of tubular cell degeneration, cytoplasmic vacuole formation, hemorrhage and tubular dilatation (P = 0.001, P = 0.017, P = 0.001, P = 0.001 respectively). There was a significant difference with regards to HSP-70 stain (P = 0.01) in favor of G1 and G3 with respect to G2. Hepatocyte degeneration in the liver samples of G3 was significantly lower than that of G1 and G2 (P = 0.027).

 Conclusion: The findings of the current study demonstrated that montelukast has protective effects on both kidney and liver; and were confirmed   histopathologically and immunohistochemically. The protective effects of montelukast can be attributed to its potential of anti-oxidative and anti-inflammatory actions.

Kaynakça

  • 1. Welborn MB, Oldenburg HS, Hess PJ, et al. The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair. Crit Care Med 2000; 28: 3191-7.
  • 2. Budak B, Seren M, Turan NN, Sakaogullari Z, Ulus AT. The protective effects of resveratrol and L-NAME on visceral organs following aortic clamping. Ann Vasc Surg 2009; 23: 675-85.
  • 3. Walker PM. Ischemia/reperfusion injury in skeletal muscle. Ann Vasc Surg 1991; 5: 399-402.
  • 4. Bown MJ, Nicholson ML, Bell PR, Sayers RD. Cytokines and inflammatory pathways in the pathogenesis of multiple organ failure following abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2001; 22: 485-95.
  • 5. Seekamp A, Warren JS, Remick DG, Till GO, Ward PA. Requirements for tumor necrosis factor-alpha and interleukin-1 in limb ischemia/reperfusion injury and associated lung injury. The American journal of pathology 1993; 143: 453-63.
  • 6. Bao XQ, Liu GT. Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice. Cell Stress Chaperones 2008; 13: 347-55.
  • 7. Zhang K, Zhao T, Huang X, et al. Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization to acute hypobaric hypoxia in mouse brain. Cell Stress Chaperones 2009;14: 407-15.
  • 8. Latchman DS. Heat shock proteins and cardiac protection. Cardiovasc Res 2001; 51: 637-46.
  • 9. D DMosser, A W Caron, L Bourget, C Denis-Larose, B Massie. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 1997; 17: 5317-27.
  • 10. Fujibayashi T, Hashimoto N, Jijiwa M, Hasegawa Y, Kojima T, Ishiguro N. Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model. BMC Pulm Med 2009; 9: 45.
  • 11. Choudhury S, Bae S, Ke Q, Lee JY, Kim J, Kang PM. Mitochondria to nucleus translocation of AIF in mice lacking Hsp70 during ischemia/reperfusion. Basic Res Cardiol 2011; 106: 397-407.
  • 12. Moreland DB, Soloniuk DS, Feldman MJ. Leukotrienes in experimental spinal cord injury. Surg Neurol 1989; 31: 277-80.
  • 13. Sener G, Sehirli O, Velioğlu-Oğünç A, et al. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res 2006; 54: 65-71.
  • 14. Damtew B, Marino JA, Fratianne RB, Spagnuolo PJ. Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury. J Lab Clin Med 1993; 121: 328-36.
  • 15. Wallace JL, Beck PL, Morris GP. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage? Am J Physiol 1988; 254:G117-23.
  • 16. Rashmitha N ST, Srinivas CH, Srinivas N, et al. A validated RP-HPLC method for the determination ofimpurities in montelukast sodium. EJ Chem 2010; 7: 555-63.
  • 17. Gedik HS, Korkmaz K, Erdem H, Karakilic E, Lafci G, Ankarali H. Protective effect of heparin in the end organ ischemia/reperfusion injury of the lungs and heart. J Cardiothorac Surg 2012; 7: 123.
  • 18. Korkmaz K, Gedik HS, Budak AB, et al. Effect of heparin on neuroprotection against spinal cord ischemia and reperfusion in rats. Eur Rev Med Pharmacol Sci 2013; 17: 522-30.
  • 19. Umehara S, Goyagi T, Nishikawa T, Tobe Y, Masaki Y. Esmolol and landiolol, selective beta1-adrenoreceptor antagonists, provide neuroprotection against spinal cord ischemia and reperfusion in rats. AnesthAnalg. 2010; 110: 1133-7.
  • 20. Yener AU, Ciçek MC, Genç SB, et al. Protective role of heparin in the injury of the liver and kidney on the experimental model of ischemia/reperfusion. J Cardiothorac Surg 2014; 9: 35.
  • 21. Harward TR, Welborn MB 3rd, Martin TD, et al. Visceral ischemia and organ dysfunction after thoracoabdominal aortic aneurysm repair. A clinical and cost analysis. Ann Surg 1996; 223: 729-34.
  • 22. Wang Z, Liu Y, Han Y, et al. Protective effects of aliskiren on ischemia-reperfusion-induced renal injury in rats. Eur J Pharmacol 2013; 718: 160-6.
  • 23. Yildar M, Aksit H, Korkut O, Ozyigit MO, Sunay B, Seyrek K. Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion injury in the rat kidney. J Surg Res 2014; 187: 683-9.
  • 24. Nicoud IB, Knox CD, Jones CM, et al. 2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake.Am J PhysiolGastrointest Liver Physiol 2007; 293: G623-30.
  • 25. Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44-84.
  • 26. Peters-Golden M, Henderson WRJr.Leukotrienes. N Engl J Med 2007; 357: 1841-54.
  • 27. Takamatsu Y, Shimada K, Chijiiwa K, Kuroki S, Yamaguchi K, Tanaka M. Role of leukotrienes on hepatic ischemia/reperfusion injury in rats. J Surg Res 2004; 119: 14-20.
  • 28. Lehr HA, Guhlmann A, Nolte D, Keppler D, Messmer K. Leukotrienes as mediators in ischemia-reperfusion injury in a microcirculation model in the hamster. J Clin Invest 1991; 87: 2036-41.
  • 29. Virchow JCJr, Faehndrich S, Nassenstein C, Bock S, Matthys H, Luttmann W. Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells. ClinExp Allergy 2001; 31: 836-44.
  • 30. Anderson R, Theron AJ, Gravett CM, Steel HC, Tintinger GR, Feldman C. Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism. Br J Pharmacol 2009; 156: 105-15.
  • 31. Cambria RP, Clouse WD, Davison JK, Dunn PF, Corey M, Dorer D. Thoracoabdominal aneurysm repair: results with 337 operations performed over a 15-year interval. Ann Surg 2002; 236: 471-9.
  • 32. Jacobs MJ, van Eps RG, de Jong DS, Schurink GW, Mochtar B. Prevention of renal failure in patients undergoing thoracoabdominal aortic aneurysm repair. J Vasc Surg 2004; 40: 1067-73.
  • 33. Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi HJ. Thoracoabdominal aortic aneurysms associated with celiac, superior mesenteric, and renal artery occlusive disease: methods and analysis of results in 271 patients. J Vasc Surg 1992; 16: 378-89.
  • 34. Adembri G, Kastamoniti E, Bertolozzi I, et al. Pulmonary ınjury follows systemic ınflamatory reaction in ınfrarenal aortic surgery. Crit Care Med 2004; 9: 1170-7.
  • 35. Norwood MG, Bown MJ, Sutton AJ, Nicholson ML, Sayers RD. Interleukin 6 production during abdominal aortic aneurysm repair arises from the gastrointestinal tract and not the legs. Br J Surg 2004; 9: 1153-6.
  • 36. Donnahoo KK, Meng X, Ayala A, Cain MP, Harken AH, Meldrum DR. Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion. Immunology 2001; 102: 53-8.
  • 37. Lauriat S, Linas SL. The role of neutrophils in acute renal failure. SeminNephrol 1998; 18: 498-504.
  • 38. Ellis RJ, van der Vies SM. Molecular chaperones. Annu Rev Biochem 1991; 60: 321-47.
  • 39. Hartl FU, Martin J, Neupert W. Protein folding in the cell: the role of molecular chaperones Hsp70 and Hsp60. Annu Rev Biophys Biomol Struct 1992;21: 293-322.
  • 40. Pan LJ, Zhang ZC, Zhang ZY, et al. Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats. World J Gastroenterol 2012; 18: 356-67.
  • 41. Dawson TL, Gores GJ, Nieminen AL, Herman B, Lemasters JJ. Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes. Am J Physiol 1993; 264: C961-7.
  • 42. Kadkhodaee M, Golab F, Zahmatkesh M, Ghaznavi R, Hedayati M, Arab HA, Ostad SN, Soleimani M. Effects of different periods of renal ischemia on liver as a remote organ. World J Gastroenterol 2009; 15: 1113-8.
  • 43. Kaçmaz A, User EY, Sehirli AO, Tilki M, Ozkan S, Sener G. Protective effect of melatonin against ischemia/reperfusion-induced oxidative remote organ injury in the rat. Surg Today 2005; 35: 744-50.
  • 44. Awad AS, Kamel R, Sherief MA. Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N-1-acetyl-transferase gene expression induced by renal ischaemia-reperfusion in rats. J Pharm Pharmacol 2011; 63: 1037-42.

Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi

Yıl 2017, Cilt 8, Sayı 2, 43 - 51, 18.06.2017
https://doi.org/10.18663/tjcl.304530

Öz

Amaç: Torakoabdominal aort anevrizması cerrahisinin sebep olabildiği splanknik iskemi, karaciğer ve/veya böbrek hasarının neden olduğu ciddi postoperatif komplikasyonlarla sonuçlanabilir. Bu çalışmada seçici tersinir bir CysLT1 reseptör antagonisti olan montelukastın, aortanın geçici oklüzyonuyla yaratılan böbrek ve karaciğer iskemi-reperfüzyon (I/R) hasarı üzerindeki koruyucu etkisini incelemek için tasarlandı.

 Gereç ve Yöntemler: Yirmi bir erkek Sprague-Dawley tipi sıçan, rasgele üç gruba (her grupta n=7) ayrıldı; G1 (aort oklüzyonu ve montelukast uygulaması yok), G2 (45 dakika aort oklüzyonu; montelukast uygulması yok) ve G3 (45 dakika aort oklüzyonu, 10 mg/kg montelukast uygulaması). Reperfüzyonun 48. saatinde böbrek ve karaciğerden alınan doku örneklerinden histopatolojik değerlendirme ve HSP 70, interlökin-6 ve miyeloperoksidaz (MPO) ile immünohistokimyasal boyama yapıldı.

 Bulgular: Böbrekten alınan doku örnekleri tübüler hücre dejenerasyonu, sitoplazmik vakuol formasyonu, hemoraji ve tübüler dilatasyon açısındna incelendi ve gruplar arasında istatistiksel olarak anlamlı fark bulundu (P = 0.001, P = 0.017, P = 0.001). G1 ve G3 gruplarında HSP-70 ile boyanmada G2 ye göre anlamlı fark saptandı (P = 0.001). G3 karaciğer örneklerinde hepatosit dejenerasyonu G1 ve G2 den anlamlı olarak düşüktü (P = 0.027).

 Sonuçlar: Yapılan çalışmanın bulguları, montelukastın böbrek ve karaciğer üzerinde koruyucu etkileri olduğunu histopatolojik ve immünohistokimyasal olarak göstermiştir. Montelukastın koruyucu etkileri, ilacın antioksidan ve antiinflamatuar etkilerine bağlanabilir. 

Kaynakça

  • 1. Welborn MB, Oldenburg HS, Hess PJ, et al. The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair. Crit Care Med 2000; 28: 3191-7.
  • 2. Budak B, Seren M, Turan NN, Sakaogullari Z, Ulus AT. The protective effects of resveratrol and L-NAME on visceral organs following aortic clamping. Ann Vasc Surg 2009; 23: 675-85.
  • 3. Walker PM. Ischemia/reperfusion injury in skeletal muscle. Ann Vasc Surg 1991; 5: 399-402.
  • 4. Bown MJ, Nicholson ML, Bell PR, Sayers RD. Cytokines and inflammatory pathways in the pathogenesis of multiple organ failure following abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2001; 22: 485-95.
  • 5. Seekamp A, Warren JS, Remick DG, Till GO, Ward PA. Requirements for tumor necrosis factor-alpha and interleukin-1 in limb ischemia/reperfusion injury and associated lung injury. The American journal of pathology 1993; 143: 453-63.
  • 6. Bao XQ, Liu GT. Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice. Cell Stress Chaperones 2008; 13: 347-55.
  • 7. Zhang K, Zhao T, Huang X, et al. Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization to acute hypobaric hypoxia in mouse brain. Cell Stress Chaperones 2009;14: 407-15.
  • 8. Latchman DS. Heat shock proteins and cardiac protection. Cardiovasc Res 2001; 51: 637-46.
  • 9. D DMosser, A W Caron, L Bourget, C Denis-Larose, B Massie. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 1997; 17: 5317-27.
  • 10. Fujibayashi T, Hashimoto N, Jijiwa M, Hasegawa Y, Kojima T, Ishiguro N. Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model. BMC Pulm Med 2009; 9: 45.
  • 11. Choudhury S, Bae S, Ke Q, Lee JY, Kim J, Kang PM. Mitochondria to nucleus translocation of AIF in mice lacking Hsp70 during ischemia/reperfusion. Basic Res Cardiol 2011; 106: 397-407.
  • 12. Moreland DB, Soloniuk DS, Feldman MJ. Leukotrienes in experimental spinal cord injury. Surg Neurol 1989; 31: 277-80.
  • 13. Sener G, Sehirli O, Velioğlu-Oğünç A, et al. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res 2006; 54: 65-71.
  • 14. Damtew B, Marino JA, Fratianne RB, Spagnuolo PJ. Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury. J Lab Clin Med 1993; 121: 328-36.
  • 15. Wallace JL, Beck PL, Morris GP. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage? Am J Physiol 1988; 254:G117-23.
  • 16. Rashmitha N ST, Srinivas CH, Srinivas N, et al. A validated RP-HPLC method for the determination ofimpurities in montelukast sodium. EJ Chem 2010; 7: 555-63.
  • 17. Gedik HS, Korkmaz K, Erdem H, Karakilic E, Lafci G, Ankarali H. Protective effect of heparin in the end organ ischemia/reperfusion injury of the lungs and heart. J Cardiothorac Surg 2012; 7: 123.
  • 18. Korkmaz K, Gedik HS, Budak AB, et al. Effect of heparin on neuroprotection against spinal cord ischemia and reperfusion in rats. Eur Rev Med Pharmacol Sci 2013; 17: 522-30.
  • 19. Umehara S, Goyagi T, Nishikawa T, Tobe Y, Masaki Y. Esmolol and landiolol, selective beta1-adrenoreceptor antagonists, provide neuroprotection against spinal cord ischemia and reperfusion in rats. AnesthAnalg. 2010; 110: 1133-7.
  • 20. Yener AU, Ciçek MC, Genç SB, et al. Protective role of heparin in the injury of the liver and kidney on the experimental model of ischemia/reperfusion. J Cardiothorac Surg 2014; 9: 35.
  • 21. Harward TR, Welborn MB 3rd, Martin TD, et al. Visceral ischemia and organ dysfunction after thoracoabdominal aortic aneurysm repair. A clinical and cost analysis. Ann Surg 1996; 223: 729-34.
  • 22. Wang Z, Liu Y, Han Y, et al. Protective effects of aliskiren on ischemia-reperfusion-induced renal injury in rats. Eur J Pharmacol 2013; 718: 160-6.
  • 23. Yildar M, Aksit H, Korkut O, Ozyigit MO, Sunay B, Seyrek K. Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion injury in the rat kidney. J Surg Res 2014; 187: 683-9.
  • 24. Nicoud IB, Knox CD, Jones CM, et al. 2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake.Am J PhysiolGastrointest Liver Physiol 2007; 293: G623-30.
  • 25. Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44-84.
  • 26. Peters-Golden M, Henderson WRJr.Leukotrienes. N Engl J Med 2007; 357: 1841-54.
  • 27. Takamatsu Y, Shimada K, Chijiiwa K, Kuroki S, Yamaguchi K, Tanaka M. Role of leukotrienes on hepatic ischemia/reperfusion injury in rats. J Surg Res 2004; 119: 14-20.
  • 28. Lehr HA, Guhlmann A, Nolte D, Keppler D, Messmer K. Leukotrienes as mediators in ischemia-reperfusion injury in a microcirculation model in the hamster. J Clin Invest 1991; 87: 2036-41.
  • 29. Virchow JCJr, Faehndrich S, Nassenstein C, Bock S, Matthys H, Luttmann W. Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells. ClinExp Allergy 2001; 31: 836-44.
  • 30. Anderson R, Theron AJ, Gravett CM, Steel HC, Tintinger GR, Feldman C. Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism. Br J Pharmacol 2009; 156: 105-15.
  • 31. Cambria RP, Clouse WD, Davison JK, Dunn PF, Corey M, Dorer D. Thoracoabdominal aneurysm repair: results with 337 operations performed over a 15-year interval. Ann Surg 2002; 236: 471-9.
  • 32. Jacobs MJ, van Eps RG, de Jong DS, Schurink GW, Mochtar B. Prevention of renal failure in patients undergoing thoracoabdominal aortic aneurysm repair. J Vasc Surg 2004; 40: 1067-73.
  • 33. Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi HJ. Thoracoabdominal aortic aneurysms associated with celiac, superior mesenteric, and renal artery occlusive disease: methods and analysis of results in 271 patients. J Vasc Surg 1992; 16: 378-89.
  • 34. Adembri G, Kastamoniti E, Bertolozzi I, et al. Pulmonary ınjury follows systemic ınflamatory reaction in ınfrarenal aortic surgery. Crit Care Med 2004; 9: 1170-7.
  • 35. Norwood MG, Bown MJ, Sutton AJ, Nicholson ML, Sayers RD. Interleukin 6 production during abdominal aortic aneurysm repair arises from the gastrointestinal tract and not the legs. Br J Surg 2004; 9: 1153-6.
  • 36. Donnahoo KK, Meng X, Ayala A, Cain MP, Harken AH, Meldrum DR. Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion. Immunology 2001; 102: 53-8.
  • 37. Lauriat S, Linas SL. The role of neutrophils in acute renal failure. SeminNephrol 1998; 18: 498-504.
  • 38. Ellis RJ, van der Vies SM. Molecular chaperones. Annu Rev Biochem 1991; 60: 321-47.
  • 39. Hartl FU, Martin J, Neupert W. Protein folding in the cell: the role of molecular chaperones Hsp70 and Hsp60. Annu Rev Biophys Biomol Struct 1992;21: 293-322.
  • 40. Pan LJ, Zhang ZC, Zhang ZY, et al. Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats. World J Gastroenterol 2012; 18: 356-67.
  • 41. Dawson TL, Gores GJ, Nieminen AL, Herman B, Lemasters JJ. Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes. Am J Physiol 1993; 264: C961-7.
  • 42. Kadkhodaee M, Golab F, Zahmatkesh M, Ghaznavi R, Hedayati M, Arab HA, Ostad SN, Soleimani M. Effects of different periods of renal ischemia on liver as a remote organ. World J Gastroenterol 2009; 15: 1113-8.
  • 43. Kaçmaz A, User EY, Sehirli AO, Tilki M, Ozkan S, Sener G. Protective effect of melatonin against ischemia/reperfusion-induced oxidative remote organ injury in the rat. Surg Today 2005; 35: 744-50.
  • 44. Awad AS, Kamel R, Sherief MA. Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N-1-acetyl-transferase gene expression induced by renal ischaemia-reperfusion in rats. J Pharm Pharmacol 2011; 63: 1037-42.

Ayrıntılar

Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Özgün Makale
Yazarlar

Ali Baran BUDAK Bu kişi benim


Kemal KORKMAZ Bu kişi benim


Hikmet Selçuk GEDİK Bu kişi benim


Gökhan LAFÇI Bu kişi benim


Ertuğrul KAYA Bu kişi benim


Handan ANKARALI Bu kişi benim


Serdar GÜNAYDIN

Yayımlanma Tarihi 18 Haziran 2017
Yayınlandığı Sayı Yıl 2017, Cilt 8, Sayı 2

Kaynak Göster

Bibtex @araştırma makalesi { tjcl304530, journal = {Turkish Journal of Clinics and Laboratory}, issn = {}, eissn = {2149-8296}, address = {}, publisher = {DNT Ortadoğu Yayıncılık A.Ş.}, year = {2017}, volume = {8}, pages = {43 - 51}, doi = {10.18663/tjcl.304530}, title = {Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi}, key = {cite}, author = {Budak, Ali Baran and Korkmaz, Kemal and Gedik, Hikmet Selçuk and Lafçı, Gökhan and Kaya, Ertuğrul and Ankaralı, Handan and Günaydın, Serdar} }
APA Budak, A. B. , Korkmaz, K. , Gedik, H. S. , Lafçı, G. , Kaya, E. , Ankaralı, H. & Günaydın, S. (2017). Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi . Turkish Journal of Clinics and Laboratory , 8 (2) , 43-51 . DOI: 10.18663/tjcl.304530
MLA Budak, A. B. , Korkmaz, K. , Gedik, H. S. , Lafçı, G. , Kaya, E. , Ankaralı, H. , Günaydın, S. "Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi" . Turkish Journal of Clinics and Laboratory 8 (2017 ): 43-51 <https://dergipark.org.tr/tr/pub/tjcl/issue/29774/304530>
Chicago Budak, A. B. , Korkmaz, K. , Gedik, H. S. , Lafçı, G. , Kaya, E. , Ankaralı, H. , Günaydın, S. "Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi". Turkish Journal of Clinics and Laboratory 8 (2017 ): 43-51
RIS TY - JOUR T1 - Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi AU - Ali Baran Budak , Kemal Korkmaz , Hikmet Selçuk Gedik , Gökhan Lafçı , Ertuğrul Kaya , Handan Ankaralı , Serdar Günaydın Y1 - 2017 PY - 2017 N1 - doi: 10.18663/tjcl.304530 DO - 10.18663/tjcl.304530 T2 - Turkish Journal of Clinics and Laboratory JF - Journal JO - JOR SP - 43 EP - 51 VL - 8 IS - 2 SN - -2149-8296 M3 - doi: 10.18663/tjcl.304530 UR - https://doi.org/10.18663/tjcl.304530 Y2 - 2016 ER -
EndNote %0 Turkish Journal of Clinics and Laboratory Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi %A Ali Baran Budak , Kemal Korkmaz , Hikmet Selçuk Gedik , Gökhan Lafçı , Ertuğrul Kaya , Handan Ankaralı , Serdar Günaydın %T Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi %D 2017 %J Turkish Journal of Clinics and Laboratory %P -2149-8296 %V 8 %N 2 %R doi: 10.18663/tjcl.304530 %U 10.18663/tjcl.304530
ISNAD Budak, Ali Baran , Korkmaz, Kemal , Gedik, Hikmet Selçuk , Lafçı, Gökhan , Kaya, Ertuğrul , Ankaralı, Handan , Günaydın, Serdar . "Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi". Turkish Journal of Clinics and Laboratory 8 / 2 (Haziran 2017): 43-51 . https://doi.org/10.18663/tjcl.304530
AMA Budak A. B. , Korkmaz K. , Gedik H. S. , Lafçı G. , Kaya E. , Ankaralı H. , Günaydın S. Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi. TJCL. 2017; 8(2): 43-51.
Vancouver Budak A. B. , Korkmaz K. , Gedik H. S. , Lafçı G. , Kaya E. , Ankaralı H. , Günaydın S. Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi. Turkish Journal of Clinics and Laboratory. 2017; 8(2): 43-51.
IEEE A. B. Budak , K. Korkmaz , H. S. Gedik , G. Lafçı , E. Kaya , H. Ankaralı ve S. Günaydın , "Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi", Turkish Journal of Clinics and Laboratory, c. 8, sayı. 2, ss. 43-51, Haz. 2017, doi:10.18663/tjcl.304530


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