Yıl: 2021 Cilt: 27 Sayı: 4 Sayfa Aralığı: 381 - 388 Metin Dili: İngilizce DOI: 10.14744/tjtes.2020.81782 İndeks Tarihi: 18-05-2022

A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury

Öz:
BACKGROUND: Ischemia-reperfusion injury (IRI) is cellular damage that emerges from re-oxygenation of a hypoxic organ. In the present study, we aimed to examine the effects of a combination of levosimendan, an inotropic agent, and N-Acetylcysteine, the precursor of antioxidants and glutathione, in an experimental liver IRI model. METHODS: In this study, 38 rats were randomly divided into five groups. Before the ischemia, study arms were given physiological saline solution, N-Acetylcysteine (NAS), levosimendan or a combination of NAS+levosimendan in a predetermined amount and duration, and the infusion was continued until the end of this study. The hepatic pedicle was occluded using an atraumatic vein clamp, and 60 minutes of ischemia was achieved. The clamp was then opened and 60 minutes of reperfusion was ensured. Liver tissue samples were obtained after sacrifice, and tissue malondialdehyde (MDA) and myeloperoxidase (MPO) levels were determined. Serum Tumor Necrosis Factor (TNF)-α, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and MPO levels of blood samples were also measured. RESULTS: Among the histopathological changes in the liver tissue after IRI, differences between groups were statistically significant in the injury scoring system based on congestion, vacuolization and necrosis levels. Histopathological injury score, plasma MPO, AST, ALT, tissue MPO and tissue MDA values were statistically significantly lower in the treatment groups, prominently in the levosimendan and NAS combination group concerning liver histopathological damage. CONCLUSION: The use of a levosimendan plus NAS combination in liver IRI markedly suppressed inflammation and oxidative stress and significantly reduced liver ischemia-reperfusion injury and can be recommended for decreasing IRI instead of single agent use of levosimendan or NAS.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
2
4
2
  • 1. Toledo-Pereyra LH, Simmons RL, Najarian JS. Protection of the ischemic liver by donor pretreatment before transplantation. Am J Surg 1975;129:513–7.
  • 2. Tredger JM. Ischaemia-reperfusion injury of the liver: treatment in theory and in practice. Biofactors 1998;8:161–4.
  • 3. Jamali IN, Kersten JR, Pagel PS, Hettrick DA, Warltier DC. Intracoronary levosimendan enhances contractile function of stunned myocardium. Anesth Analg 1997;85:23–9.
  • 4. Masahiro A, Yoshiharu T, Satoshi I. Comparison of the protective effect of n-acetylcysteine by different treatments on rat myocardial ischemia-reperfusion injury. J Pharmacol Sci 2008;106:571–7.
  • 5. Grace PA. Ischaemia-reperfusion injury. Br J Surg 1994;81:637–47.
  • 6. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000;190:255–66.
  • 7. Wang CY, Ni Y, Liu Y, Huang ZH, Zhang MJ, Zhan YQ, et al. Mild hypothermia protects liver against ischemia and reperfusion injury. World J Gastroenterol 2005;11:3005-7.
  • 8. Byrka-Owczarek K, Steplewska-Mazur K, Krasoń M, Bohosiewicz J, Koszutski T, Wojtynek G. The evaluation of the protective action of antioxidants on small intestine of rabbits experimentally injured by ischemia and reperfusion. J Pediatr Surg 2004;39:1226–9.
  • 9. Chavez-Cartaya R, Jamieson NV, Ramirez P, Marin J, Pino-Chavez G. Free radical scavengers to prevent reperfusion injury following experimental warm liver ischaemia. Is there a real physiological benefit?. Transpl Int 1999;12:213–21.
  • 10. Montero EF, Quireze C Jr, d’Oliveira DM. Bile duct exclusion from selective vascular inflow occlusion in rat liver: role of ischemic preconditioning and N-acetylcysteine on hepatic reperfusion injury. Transplant Proc 2005;37:425–7.
  • 11. Mojzis J, Hegedüsová R, Mirossay L. Role of mucus in ischemia/reperfusion-induced gastric mucosal injury in rats. Physiol Res 2000;49:441–6.
  • 12. Cuzzocrea S, Mazzon E, Costantino G, Serraino I, De Sarro A, Caputi AP. Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury. Cardiovasc Res 2000;47:537–48.
  • 13. Lee EJS, da Silva SM, Simões MJ, Montero EFS. Effect of N- acetylcysteine in liver ischemia-reperfusion injury after 30% hepatectomy in mice. Acta Cir Bras 2012;27:346–9.
  • 14. Oktar GL, Demir Amac N, Elmas C, Arslan M, Goktas G, Iriz E, et al. The histopathological effects of levosimendan on liver injury induced by myocardial ischemia and reperfusion. Bratisl Lek Listy 2015;116:241–7.
  • 15. Crockett ET, Galligan JJ, Uhal BD, Harkema J, Roth R, Pandya K. Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists. BMC Clin Pathol 2006;6:3.
  • 16. Serracino-Inglott F, Virlos IT, Habib NA, Williamson RC, Mathie RT. Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase. BMC Gastroenterol 2002;2:22.
  • 17. Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, Cejalvo D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation 1993;55:1265–72.
  • 18. Yabe Y, Kobayashi N, Nishihashi T, Takahashi R, Nishikawa M, Takakura Y, et al. Prevention of neutrophil-mediated hepatic ischemia/reperfusion injury by superoxide dismutase and catalase derivatives. J Pharmacol Exp Ther 2001;298:894–9.
  • 19. Henderson JM. Liver transplantation and rejection: an overview. Hepatogastroenterology 1999;46:1482–4.
  • 20. Peralta C, Prats N, Xaus C, Gelpí E, Roselló-Catafau J. Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia-reperfusion in the rat. Hepatology 1999;30:1481–9.
  • 21. Strieter RM, Kunkel SL, Bone RC. Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med 1993;21:S447–63.
  • 22. Katircioglu SF, Seren M, Parlar AI, Turan NN, Manavbasi Y, Aydog G, et al. Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping. J Card Surg 2008;23:44–8.
  • 23. Sener G, Tosun O, Sehirli AO, Kaçmaz A, Arbak S, Ersoy Y, et al. Melatonin and N-acetylcysteine have beneficial effects during hepatic ischemia and reperfusion. Life Sci 2003;72:2707–18.
  • 24. Semenzato G. Tumour necrosis factor: a cytokine with multiple biological activities. Br J Cancer 1990;61:354–61.
  • 25. Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 1990;24:285–95.
  • 26. Paraskevaidis IA, Parissis JT, Th Kremastinos D. Anti-inflammatory and anti-apoptotic effects of levosimendan in decompensated heart failure: a novel mechanism of drug-induced improvement in contractile performance of the failing heart. Curr Med Chem Cardiovasc Hematol Agents 2005;3:243–7.
  • 27. Kaptan K, Erinç K, Ifran A, Yildirim V, Uzun M, Beyan C, et al. Levosimendan has an inhibitory effect on platelet function. Am J Hematol 2008;83:46–9
APA SUAKITICI S, güven b, Tanoglu A, Özkan S (2021). A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. , 381 - 388. 10.14744/tjtes.2020.81782
Chicago SUAKITICI Serkan,güven bülent barış,Tanoglu Alpaslan,Özkan Sezai A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. (2021): 381 - 388. 10.14744/tjtes.2020.81782
MLA SUAKITICI Serkan,güven bülent barış,Tanoglu Alpaslan,Özkan Sezai A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. , 2021, ss.381 - 388. 10.14744/tjtes.2020.81782
AMA SUAKITICI S,güven b,Tanoglu A,Özkan S A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. . 2021; 381 - 388. 10.14744/tjtes.2020.81782
Vancouver SUAKITICI S,güven b,Tanoglu A,Özkan S A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. . 2021; 381 - 388. 10.14744/tjtes.2020.81782
IEEE SUAKITICI S,güven b,Tanoglu A,Özkan S "A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury." , ss.381 - 388, 2021. 10.14744/tjtes.2020.81782
ISNAD SUAKITICI, Serkan vd. "A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury". (2021), 381-388. https://doi.org/10.14744/tjtes.2020.81782
APA SUAKITICI S, güven b, Tanoglu A, Özkan S (2021). A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. Ulusal Travma ve Acil Cerrahi Dergisi, 27(4), 381 - 388. 10.14744/tjtes.2020.81782
Chicago SUAKITICI Serkan,güven bülent barış,Tanoglu Alpaslan,Özkan Sezai A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. Ulusal Travma ve Acil Cerrahi Dergisi 27, no.4 (2021): 381 - 388. 10.14744/tjtes.2020.81782
MLA SUAKITICI Serkan,güven bülent barış,Tanoglu Alpaslan,Özkan Sezai A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. Ulusal Travma ve Acil Cerrahi Dergisi, vol.27, no.4, 2021, ss.381 - 388. 10.14744/tjtes.2020.81782
AMA SUAKITICI S,güven b,Tanoglu A,Özkan S A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. Ulusal Travma ve Acil Cerrahi Dergisi. 2021; 27(4): 381 - 388. 10.14744/tjtes.2020.81782
Vancouver SUAKITICI S,güven b,Tanoglu A,Özkan S A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury. Ulusal Travma ve Acil Cerrahi Dergisi. 2021; 27(4): 381 - 388. 10.14744/tjtes.2020.81782
IEEE SUAKITICI S,güven b,Tanoglu A,Özkan S "A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury." Ulusal Travma ve Acil Cerrahi Dergisi, 27, ss.381 - 388, 2021. 10.14744/tjtes.2020.81782
ISNAD SUAKITICI, Serkan vd. "A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury". Ulusal Travma ve Acil Cerrahi Dergisi 27/4 (2021), 381-388. https://doi.org/10.14744/tjtes.2020.81782