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Comparison of effects of melatonin, pentoxifylline and dimethyl sulfoxide in experimental liver ischemia-reperfusion injury by three different methods

Year 2019, Volume: 5 Issue: 1, 148 - 158, 04.01.2019
https://doi.org/10.18621/eurj.421296

Abstract

Objectives: Liver transplantation is increasingly being used in
the treatment of end-stage liver disease. Ischemia-reperfusion injury is one of
the major problems encountered in transplantation. In this study, we aimed to
compare the effects of melatonin, pentoxifylline, and
dimethyl sulfoxide (DMSO), in hepatic ischemia-reperfusion injury with different methods
such as biochemical/ultrastructural changes and hepatobiliary scintigraphy.

Methods: Thirty rabbits were used in the Laboratory of
Experimental Animals of Trakya University under appropriate conditions. Sham
laparotomy and only ischemia reperfusion group were planned. They were used
melatonin, pentoxifylline, and DMSO after ischemia-reperfusion in the other three groups. 6
rabbits were randomly selected for each group. Rabbits in all groups were
subjected to liver scintigraphy. Following scintigraphy, 2 cm2 of
liver tissue was removed to examining for liver antioxidant enzyme levels (superoxide
dismutase [SOD] and glutathione peroxidase [GPx]) and for liver electron
microscopy.

Results: Pentoxifylline and melatonin protected significantly
uptake and excretion functions in liver scintigraphy. When the effects of all
three substances were examined by electron microscopy, it was found that the
three substances protected the liver from the effects of ischemia-reperfusion damage
at varying rates. All three agents were found to protect SOD and GPx from
falling in various amounts.







Conclusions: Studies to prevent ischemia-reperfusion injury, which
may develop as a result of the Pringle maneuver applied to liver
transplantations as well as to liver resections or liver injuries, still
maintain their popularity. In our study, the effects of agents were identified
in three different ways. Ischemia-reperfusion injury-reducing effect of
pentoxifylline gave parallel results with three methods. 

References

  • [1] Pringle JG. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908;48:541-9.
  • [2] Park SW, Lee SM. Antioksidant and prooksidant properties of ascorbic acid on hepatic dysfunction induced by cold ischemia-reperfusion, Eur J Pharmacol 2008;580:401-6.
  • [3] Grossine E, Pollesello P, Bellofatto K, Siguado L, Farruggio S, Origlia V, et al. Protective effects elicited by levosimendan against liver ischemia/reperfusion injury in anesthetized rats. Liver Transpl 2014;20:361-75.
  • [4] Lee SM, Park MJ, Cho TS, Clemens MG. Hepatic injury and lipid peroxidation during ischemia and reperfusion. Shock 2000;13:279-84.
  • [5] Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology 2014;29:325-33.
  • [6] Hatipoglu AR, Temiz E, Yuksel M, Hoscoskun Z, Coskun I, Huseyinova G. The comparison of electron microscopy and scintigraphy in determining the protective effect of DMSO on ischemiae/reperfusion injury in rats. Hepatogastroenterology 2001;48:798-802.
  • [7] El-Ghoneimi A. Inhibition of tumor necrosis factor alpha gene transcription by pentoxifylline reduces normothermic liver ischemia-reperfusion injury in rats. Tranplant Proc 2007;39:1761-4.
  • [8] Wang WY, Taki Y, Monimoto T, Nishihira T, Yokoo N, Jikko A. Effects of partial ischemia and reflow on mitochondrial metabolism in rat liver. Eur Surg Res 1988;20:181-9.
  • [9] Halliwell B. Oxidative stress, nutrition health, exprimental strategies for optimization of nutritional antioxidant intake in humans. Free Radic Res 1996;25:57-74.
  • [10] Valko M, Jomova K, Rhodes CJ, Kuca K, Musilek K. Redox‑ and non‑redox‑metal‑induced formation of free radicals and their role in human disease. Arch Toxicol 2016;90:1-37.
  • [11] Barber DA, Harris SR. Oxygen free radicals and antioxidants: a review. Am Pharm 1994;34:26-35.
  • [12] Romani F, Vertamati M, Frangi M, Aseni P, Monti R, Codeghini A, et al. Effects of superoksid dismutase on liver ischemia reperfusion injury in the rat: a biochemical monitoring. Eur Surg Res1988:20:335-40.
  • [13] Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:15-21.
  • [14] McCord JM, Edeas MA. SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother 2005;59:139-42.
  • [15] Hatipoglu A, Turkyılmaz Z, Mert S. The effects of melatonin on postoperative intraabdominal adhesion formation. Yonsei Med J 2007;48:659-64.
  • [16] Tan DX, Chen LD, Poeggeler B, Manchrter LC, Reiter RJ. Melatonin: a potent, endogenous hidroxyl radical scavenger. Endocr J 1993;1:57-60.
  • [17] Reiter RJ. Melatonin: lowering the high price of free radicals. News Physiol Sci 2000;15:246-50.
  • [18] Baykara B, Tekmen I, Pekcetin C, Ulukus C, Tuncel P, Sagol O, et al. The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver. Acta Histochem 2009;111:42-51.
  • [19] Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in the antioxidativedefence system: reactions and products. Biol Signals Recept 2000;9:137-59.
  • [20] Sewerynek E, Reiter RJ, Melchiorri D, Ortiz GG, Lewinski A. Oxidative damage in the liver induced by ischemia-reperfusion: protection by melatonin. Hepatogastroenterology 1996;43:898-905.
  • [21] Kim SH, Lee SM. Cytoprotective effects of melatonin against necrosis and apoptosis induced by ischemia/reperfusion injury in rat liver. J Pineal Res 2008;44:165-71.
  • [22] Aktoz T, Aydoğdu N, Alagol B, Yalçın O, Hüseyinova G, Atakan IH. The protective effects of melatonin and vitamin E against renal ischemia-reperfusion injury in rats. Ren Fail 2007;29:535-42.
  • [23] Adams GA, Dhar A, Shukla SD, Silver D. Effects of pentoxifylline on tissue injury and platelet activating factor production during ischemia-reperfusion injury. J Vasc Surg 1995;21:742-8.
  • [24] Genoves P, Garcia D, Cejalvo D, Martin A, Zaragoza C,Toledo AH, et al. Pentoxifylline in liver ischemia and reperfusion. J Invest Surg 2014;27:114-24.
  • [25] Dinckan A, Sahin E, Oguz M, Emek K, Gumuslu S. The effect of pentoxifylline on oxidative stress in CO2 pneumoperitoneum.Surg Endosc 2009;23:534-8.
  • [26] Hammerman C, Goldschimidt D, Caplan MS, Eidelman AY, Branki D, Hochman A. Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase. J Pediatr Gastroenterol Nutr 1999;29:69-74.
  • [27] Inal M, Kanbak G, Adali M. Prevention of ischemia-reperfusion-induced oxidative injury in liver by allopurinol and pentoxifylline. Transplantationsmedizin 2006;18:29-32.
  • [28] Petrowsky H, Breitenstein S, Slankamenac K, Vetter D, Lehmann K, Heinrich S, et al. Effects of Pentoxifylline on liver regeneration: A double-blinded, randomized; controlled trial in 101 patients undergoing major liver resection. Ann Surg 2010;252:813-22.
  • [29] Akyurek N, Kafali EM, Muhtaroglu S. The effects of dimethylsulfoxide on experimental hepatic ischemia. Swiss Surg 2000;6:23-7.
  • [30] Nishihara G, Sakemi T, Ikeda Y. Multiple organ failure associated with dimethyl sulfoxide and hiroxyethylstrach in autologous blood stem cell transplantation. Nephron 1996;72:356-7.
  • [31] Sahin M, Avsar FM, Ozel H, Topalaoglu S, Yilmaz B, Pasaoglu H, et al. The effects of dimethyl sulfoxide on liver damage caused by ischemia-reperfusion. Tranplant Proc 2004;36:2590-2.
  • [32] Loken MK, Ascher NL, Boudreau RJ, Najarian JS. Scintigraphic evaluation of liver transplant function. J Nucl Med 1986;27:451-9.
  • [33] Graaf W, Bennink R, Vetelainen R, Guulik T. Nuclear imaging techniques for the assessment of hepatic function in liver surgery and transplantation. J Nucl Med 2010;51:742-52.
  • [34] Ekman M, Fjalling M, Holmberg S, Person H. IODIDA clearance rate: a method for measuring hepatocyte uptake function. Tranplant Proc1992;24:387-8.
  • [35] Vetelainen RL, Bennink RJ, De Bruin K, Van Vliet A, Van Gulik TM. Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model. Eur J Nucl Med Mol Imaging 2006;33:1107-14.
  • [36] Kurzawinski TR, Selves L, Farouk M, Dooley J, Hilson A, Buscombe JR, et al. Prospective study of hepatobiliaryscintigraphy and endoscopic cholangiography for the detection of early biliary complications after orthotopic liver transplantation. Br J Surg 1997;84:620-3.
  • [37] Brunot B, Petras S, Germain P, Vinee P, Constantinesco A. Biopsy and quantitative hepatobiliaryscintigraphy in the evaluation of liver transplantation. J Nucl Med 1994;35:1321-7.
  • [38] Kim JS, Moon DH, Lee SG, Lee YJ, Park KM, Hwang S, et al. The usefulness of hepatobiliaryscintigraphy in the diagnosis of complications after adult-to-adult living donor liver transplantation. Eur J Nucl Med Mol Imaging 2002;29:473-9.
  • [39] Tagge EP, Champbell D Jr, Reichie R. Quantitative hepatic scintigrapy to evaluate ischemic-reperfusion injury in porcine liver transplantation. Tranplant Proc 1987;1:1095-7.
  • [40] Kuni CC, Engeler CM, Nakhieh RE, Du Cret RP, Boudreau RJ. Correlation of technetium-99m-DISIDA hepatobiliary studies with biopsies in liver transplant patients. J Nucl Med 1991;32:1545-7.
Year 2019, Volume: 5 Issue: 1, 148 - 158, 04.01.2019
https://doi.org/10.18621/eurj.421296

Abstract

References

  • [1] Pringle JG. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908;48:541-9.
  • [2] Park SW, Lee SM. Antioksidant and prooksidant properties of ascorbic acid on hepatic dysfunction induced by cold ischemia-reperfusion, Eur J Pharmacol 2008;580:401-6.
  • [3] Grossine E, Pollesello P, Bellofatto K, Siguado L, Farruggio S, Origlia V, et al. Protective effects elicited by levosimendan against liver ischemia/reperfusion injury in anesthetized rats. Liver Transpl 2014;20:361-75.
  • [4] Lee SM, Park MJ, Cho TS, Clemens MG. Hepatic injury and lipid peroxidation during ischemia and reperfusion. Shock 2000;13:279-84.
  • [5] Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology 2014;29:325-33.
  • [6] Hatipoglu AR, Temiz E, Yuksel M, Hoscoskun Z, Coskun I, Huseyinova G. The comparison of electron microscopy and scintigraphy in determining the protective effect of DMSO on ischemiae/reperfusion injury in rats. Hepatogastroenterology 2001;48:798-802.
  • [7] El-Ghoneimi A. Inhibition of tumor necrosis factor alpha gene transcription by pentoxifylline reduces normothermic liver ischemia-reperfusion injury in rats. Tranplant Proc 2007;39:1761-4.
  • [8] Wang WY, Taki Y, Monimoto T, Nishihira T, Yokoo N, Jikko A. Effects of partial ischemia and reflow on mitochondrial metabolism in rat liver. Eur Surg Res 1988;20:181-9.
  • [9] Halliwell B. Oxidative stress, nutrition health, exprimental strategies for optimization of nutritional antioxidant intake in humans. Free Radic Res 1996;25:57-74.
  • [10] Valko M, Jomova K, Rhodes CJ, Kuca K, Musilek K. Redox‑ and non‑redox‑metal‑induced formation of free radicals and their role in human disease. Arch Toxicol 2016;90:1-37.
  • [11] Barber DA, Harris SR. Oxygen free radicals and antioxidants: a review. Am Pharm 1994;34:26-35.
  • [12] Romani F, Vertamati M, Frangi M, Aseni P, Monti R, Codeghini A, et al. Effects of superoksid dismutase on liver ischemia reperfusion injury in the rat: a biochemical monitoring. Eur Surg Res1988:20:335-40.
  • [13] Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:15-21.
  • [14] McCord JM, Edeas MA. SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother 2005;59:139-42.
  • [15] Hatipoglu A, Turkyılmaz Z, Mert S. The effects of melatonin on postoperative intraabdominal adhesion formation. Yonsei Med J 2007;48:659-64.
  • [16] Tan DX, Chen LD, Poeggeler B, Manchrter LC, Reiter RJ. Melatonin: a potent, endogenous hidroxyl radical scavenger. Endocr J 1993;1:57-60.
  • [17] Reiter RJ. Melatonin: lowering the high price of free radicals. News Physiol Sci 2000;15:246-50.
  • [18] Baykara B, Tekmen I, Pekcetin C, Ulukus C, Tuncel P, Sagol O, et al. The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver. Acta Histochem 2009;111:42-51.
  • [19] Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in the antioxidativedefence system: reactions and products. Biol Signals Recept 2000;9:137-59.
  • [20] Sewerynek E, Reiter RJ, Melchiorri D, Ortiz GG, Lewinski A. Oxidative damage in the liver induced by ischemia-reperfusion: protection by melatonin. Hepatogastroenterology 1996;43:898-905.
  • [21] Kim SH, Lee SM. Cytoprotective effects of melatonin against necrosis and apoptosis induced by ischemia/reperfusion injury in rat liver. J Pineal Res 2008;44:165-71.
  • [22] Aktoz T, Aydoğdu N, Alagol B, Yalçın O, Hüseyinova G, Atakan IH. The protective effects of melatonin and vitamin E against renal ischemia-reperfusion injury in rats. Ren Fail 2007;29:535-42.
  • [23] Adams GA, Dhar A, Shukla SD, Silver D. Effects of pentoxifylline on tissue injury and platelet activating factor production during ischemia-reperfusion injury. J Vasc Surg 1995;21:742-8.
  • [24] Genoves P, Garcia D, Cejalvo D, Martin A, Zaragoza C,Toledo AH, et al. Pentoxifylline in liver ischemia and reperfusion. J Invest Surg 2014;27:114-24.
  • [25] Dinckan A, Sahin E, Oguz M, Emek K, Gumuslu S. The effect of pentoxifylline on oxidative stress in CO2 pneumoperitoneum.Surg Endosc 2009;23:534-8.
  • [26] Hammerman C, Goldschimidt D, Caplan MS, Eidelman AY, Branki D, Hochman A. Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase. J Pediatr Gastroenterol Nutr 1999;29:69-74.
  • [27] Inal M, Kanbak G, Adali M. Prevention of ischemia-reperfusion-induced oxidative injury in liver by allopurinol and pentoxifylline. Transplantationsmedizin 2006;18:29-32.
  • [28] Petrowsky H, Breitenstein S, Slankamenac K, Vetter D, Lehmann K, Heinrich S, et al. Effects of Pentoxifylline on liver regeneration: A double-blinded, randomized; controlled trial in 101 patients undergoing major liver resection. Ann Surg 2010;252:813-22.
  • [29] Akyurek N, Kafali EM, Muhtaroglu S. The effects of dimethylsulfoxide on experimental hepatic ischemia. Swiss Surg 2000;6:23-7.
  • [30] Nishihara G, Sakemi T, Ikeda Y. Multiple organ failure associated with dimethyl sulfoxide and hiroxyethylstrach in autologous blood stem cell transplantation. Nephron 1996;72:356-7.
  • [31] Sahin M, Avsar FM, Ozel H, Topalaoglu S, Yilmaz B, Pasaoglu H, et al. The effects of dimethyl sulfoxide on liver damage caused by ischemia-reperfusion. Tranplant Proc 2004;36:2590-2.
  • [32] Loken MK, Ascher NL, Boudreau RJ, Najarian JS. Scintigraphic evaluation of liver transplant function. J Nucl Med 1986;27:451-9.
  • [33] Graaf W, Bennink R, Vetelainen R, Guulik T. Nuclear imaging techniques for the assessment of hepatic function in liver surgery and transplantation. J Nucl Med 2010;51:742-52.
  • [34] Ekman M, Fjalling M, Holmberg S, Person H. IODIDA clearance rate: a method for measuring hepatocyte uptake function. Tranplant Proc1992;24:387-8.
  • [35] Vetelainen RL, Bennink RJ, De Bruin K, Van Vliet A, Van Gulik TM. Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model. Eur J Nucl Med Mol Imaging 2006;33:1107-14.
  • [36] Kurzawinski TR, Selves L, Farouk M, Dooley J, Hilson A, Buscombe JR, et al. Prospective study of hepatobiliaryscintigraphy and endoscopic cholangiography for the detection of early biliary complications after orthotopic liver transplantation. Br J Surg 1997;84:620-3.
  • [37] Brunot B, Petras S, Germain P, Vinee P, Constantinesco A. Biopsy and quantitative hepatobiliaryscintigraphy in the evaluation of liver transplantation. J Nucl Med 1994;35:1321-7.
  • [38] Kim JS, Moon DH, Lee SG, Lee YJ, Park KM, Hwang S, et al. The usefulness of hepatobiliaryscintigraphy in the diagnosis of complications after adult-to-adult living donor liver transplantation. Eur J Nucl Med Mol Imaging 2002;29:473-9.
  • [39] Tagge EP, Champbell D Jr, Reichie R. Quantitative hepatic scintigrapy to evaluate ischemic-reperfusion injury in porcine liver transplantation. Tranplant Proc 1987;1:1095-7.
  • [40] Kuni CC, Engeler CM, Nakhieh RE, Du Cret RP, Boudreau RJ. Correlation of technetium-99m-DISIDA hepatobiliary studies with biopsies in liver transplant patients. J Nucl Med 1991;32:1545-7.
There are 40 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Articles
Authors

Zeliha Türkyılmaz 0000-0002-0012-2089

Ahmet Hatipoğlu This is me 0000-0003-2691-2529

Mahmut Yüksel 0000-0003-0159-6873

Nurettin Aydoğdu 0000-0002-6341-5137

Gülara Hüseyinova This is me 0000-0001-7941-2080

Publication Date January 4, 2019
Submission Date May 5, 2018
Acceptance Date July 4, 2018
Published in Issue Year 2019 Volume: 5 Issue: 1

Cite

AMA Türkyılmaz Z, Hatipoğlu A, Yüksel M, Aydoğdu N, Hüseyinova G. Comparison of effects of melatonin, pentoxifylline and dimethyl sulfoxide in experimental liver ischemia-reperfusion injury by three different methods. Eur Res J. January 2019;5(1):148-158. doi:10.18621/eurj.421296

e-ISSN: 2149-3189 


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