Research Article
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Year 2021, Volume: 38 Issue: 2, 66 - 71, 03.04.2021

Abstract

Supporting Institution

rdu Üniversitesi Bilimsel Araştırma Proje Başkanlığı

Project Number

TT-1501

Thanks

TT-1501 numaralı projeyi maddi açıdan destekleyen Ordu Üniversitesi Bilimsel Araştırma Proje Başkanlığına teşekkür ediyoruz.

References

  • Abdel-Salam, O.M.E., Mohammed, N.A, Sleem, A., 2011. The effects of trimetazidine on lipopolysaccharide-induced oxidative stress in mice. EXCLI J. 10(1), 162–172.
  • Alshammari, G.M., Balakrishnan, A., Chinnasamy, T., 2018. Butein protects the nonalcoholic fatty liver through mitochondrial reactive oxygen species attenuation in rats. Biofactors. 44(3), 289-298.
  • Ayyildiz, A., Ayyildiz, S., Benli, E., Erdem, H., Cirrik S., Noyan, T., et al., 2016. The effect of oral and intraurethral trimetazidine use on urethral healing. Iran J. Basic Med. Sc. 19(9), 932–939.
  • Ben-Mosbah, I., Casillas-Ramírez, A., Xaus C., Serafín, A., Roselló-Catafau, J., Peralta, C., 2006. Trimetazidine: is it a promising drug for use in steatotic grafts? World J. Gastroenterol. 12(6), 908–914.
  • Bradley, P.P., Priebat, D.A., Christensen, R.D., Rothstein, G., 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 78(3), 206-209.
  • Carmiel-Haggai, M., Cederbaum, A.I., Nieto, N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J. 19, 136–138.
  • Casillas, A., Mosbah, I.B., Ramalho, F., Roselló-Catafau, J., Peralta, C., 2006. Past and future approaches to ischemia-reperfusion lesion associated with liver transplantation. Life Sci. 79(20), 1881-1894.
  • French, S.W., Miyamoto, K., Ohta, Y., Geoffrion, Y., 2000. Pathogenesis of experimental alcoholic liver disease in the rat. Methods Achiev. Exp. Pathol. 13, 181–207.
  • Goth, L., 1992. A simple method for determination of serum catalase activation and revision of reference range. Clin. Chim. Acta. 196(2-3), 143-151.
  • Gupta, N.A., Kolachala, V.L., Jiang, R., Abramowsky, C., Shenoi, A., Kosters, A., et al., 2014. Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver. Am. J. Physiol. Gastrointest. Liver Physiol. 307(11), G1088-99.
  • Jorgačević, B., Mladenović, D., Ninković, M., Prokić, V., Stanković, M.N., Aleksić, V., et al., 2014. Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Hum. Exp. Toxicol. 33(7), 701-709.
  • Kapoor, M., Sharma, N., Sandhir, R., Nehru, B., 2018. Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion hippocampus injury in rat brain. Biomed Pharmacother. 97, 458-472.
  • Kato, H., Kuriyama, N., Duarte, S., Clavien, P.A, Busuttil, R.W., Coito, A.J., 2014. MMP-9 deficiency shelters endothelial PECAM-1 expression and enhances regeneration of steatotic livers after ischemia and reperfusion injury. J Hepatol. 60(5), 1032-1039.
  • Leghi, G.E., Domenici, F.A., Vannucchi, H., 2015. Influence of oxıdatıve stress and obesıty ın patıents wıth nonalcoholıc steatohepatıtıs. Arq. Gastroenterol. 52(3), 228-233.
  • Li, X., Liu, J., Lin, L., Wu, J.Q., Li, H.X., Sun, B.J., et.al., 2014. Traditional Chinese medicine shuang shen ning xin attenuates myocardial ischemia/reperfusion injury by preserving of mitochondrial function. Evid. Based Complement Alternat. Med. 2014:180965.
  • Liu, B., Ma, Z.Y., Wu, G., Qian, J.M., 2015. Butyrate protects rats from hepatic ischemia/reperfusion injury. Int. J. Clin. Exp. Med. 8(4), 5406–5413.
  • Mahfoudh-Boussaid, A., Zaouali, M.A., Hauet, T., Hadj-Ayed, K., Miled, A.H., Ghoul-Mazgar, S, et al., 2012. Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment. J. Biomed. Sci. 19 (1), 71.
  • Onay- Besikci, A., Özkan, S.A., 2008. Trimetazidine Revisited: A comprehensive review of the pharmacological effects and analytical techniques for the determination of trimetazidine. Cardiovasc. Ther. 26(2), 147-165.
  • Park, H.S., Jang, J.E., Ko, M.S., Woo, S.H., Kim, B.J., Kim, H.S., et al., 2016. Statins increase mitochondrial and peroxisomal fatty acid oxidation in the liver and prevent non-alcoholic steatohepatitis in mice. Diabetes Metab. J. 40(5), 376-385.
  • Prieto, I., Monsalve, M., 2017. ROS homeostasis, a key determinant in liver ischemic-preconditioning Redox Biol. 12, 1020–1025.
  • Selzner, N., Selzner, M., Jochum, W., Clavien, P.A., 2003. Ischemic preconditioning protects the steatotic mouse liver against reperfusion injury: an ATP dependent mechanism. J Hepatol. 39(1), 55-61.
  • Tao, X., Sun, X., Xu, L., Yin, L., Han, X., Qi, Y., et al., 2016. Total flavonoids from rosa laevigata michx fruit ameliorates hepatic ıschemia/reperfusion injury through inhibition of oxidative stress and inflammation in rats. Nutrients. 8(7), pii E418.
  • Tashiro, H., Kuroda, S., Mikuriya, Y., Ohdan, H., 2014. Ischemia–reperfusion injury in patients with fatty liver and the clinical impact of steatotic liver on hepatic surgery. Surg. Today. 44(9), 1611-1625.
  • Yalçın, A.D., Bisgin, A., Erbay, R.H, Oguz, O., Demir, S., Yilmaz, M., et al., 2012. Trimetazidine effect on burn-induced intestinal mucosal injury and kidney damage in rats. Int. J. Burns Trauma. 2(2), 110-117.
  • Yoo, J.J., Kim, W., Kim, M.Y., Jun, D.W., Kim, S.G., Yeon, J.E., et al., 2019. Recent research trends and updates on nonalcoholic fatty liver disease. Clin. Mol. Hepatol. 25(1), 1-11.
  • Zaouali, M.A., Panisello, A., Lopez, A., Castro, C., Folch, E., Carbonell, T., et al., 2017. GSK3β and VDAC involvement in ER stress and apoptosis modulation during orthotopic liver transplantation. Int. J. Mol. Sci.18(3), 591.

Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats

Year 2021, Volume: 38 Issue: 2, 66 - 71, 03.04.2021

Abstract

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver diseases that occur in individuals who do not consume a significant amount of alcohol, and the pathogenesis of NAFLD remains undefined. It was aimed to investigate whether the use of Trimetazidine (TMZ) could reduce warm ischemia-reperfusion (I/R) damage after liver ischemia on an experimental NAFLD model in this experimental study.
Methods: For this aim, Sprague Dawley male rats were separated into 4 groups; control group (group 1, n = 6), sham operated control grup (group 2, n = 6), warm ischemia/reperfusion group (group 3, n=10), and TMZ group (group 4, n=10, administration of TMZ (10 mg/kg) 30-min before fatty liver I/R). The serum oxidant and antioxidant biochemical markers were measured by ELISA methods. The histopathological evaluation was also performed in the hepatocytes.
Results: TMZ was caused to significantly decrease on oxidative stress markers levels which characterized myeloperoxidase (MPO) (p<0.001), nicotinamide adenine dinucleotide phosphate-oxidase (NOX) (p<0.001), and cytochrome C (Cyt-C) (p<0.001), and increase on antioxidant enzyme catalase (CAT) (p<0.001) activity as compared to group 3. However, TMZ was no caused to any significant change in other oxidant markers malondialdehyde (MDA) and 8-hydroxyguanosine (8-OHDG) levels (p> 0.05). While hepatocyte damage as a form of cell groups was observed due to I/R damage, whereas TMZ had caused positive improvements on dilatation of sinusoids, inflammation and the structural integrity of hepatic plaques.
Conclusion: Trimetazidine could be positively contributing effects to the antioxidant defense mechanism and also the survival of cells by protecting mitochondrial integrity.

Project Number

TT-1501

References

  • Abdel-Salam, O.M.E., Mohammed, N.A, Sleem, A., 2011. The effects of trimetazidine on lipopolysaccharide-induced oxidative stress in mice. EXCLI J. 10(1), 162–172.
  • Alshammari, G.M., Balakrishnan, A., Chinnasamy, T., 2018. Butein protects the nonalcoholic fatty liver through mitochondrial reactive oxygen species attenuation in rats. Biofactors. 44(3), 289-298.
  • Ayyildiz, A., Ayyildiz, S., Benli, E., Erdem, H., Cirrik S., Noyan, T., et al., 2016. The effect of oral and intraurethral trimetazidine use on urethral healing. Iran J. Basic Med. Sc. 19(9), 932–939.
  • Ben-Mosbah, I., Casillas-Ramírez, A., Xaus C., Serafín, A., Roselló-Catafau, J., Peralta, C., 2006. Trimetazidine: is it a promising drug for use in steatotic grafts? World J. Gastroenterol. 12(6), 908–914.
  • Bradley, P.P., Priebat, D.A., Christensen, R.D., Rothstein, G., 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 78(3), 206-209.
  • Carmiel-Haggai, M., Cederbaum, A.I., Nieto, N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J. 19, 136–138.
  • Casillas, A., Mosbah, I.B., Ramalho, F., Roselló-Catafau, J., Peralta, C., 2006. Past and future approaches to ischemia-reperfusion lesion associated with liver transplantation. Life Sci. 79(20), 1881-1894.
  • French, S.W., Miyamoto, K., Ohta, Y., Geoffrion, Y., 2000. Pathogenesis of experimental alcoholic liver disease in the rat. Methods Achiev. Exp. Pathol. 13, 181–207.
  • Goth, L., 1992. A simple method for determination of serum catalase activation and revision of reference range. Clin. Chim. Acta. 196(2-3), 143-151.
  • Gupta, N.A., Kolachala, V.L., Jiang, R., Abramowsky, C., Shenoi, A., Kosters, A., et al., 2014. Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver. Am. J. Physiol. Gastrointest. Liver Physiol. 307(11), G1088-99.
  • Jorgačević, B., Mladenović, D., Ninković, M., Prokić, V., Stanković, M.N., Aleksić, V., et al., 2014. Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Hum. Exp. Toxicol. 33(7), 701-709.
  • Kapoor, M., Sharma, N., Sandhir, R., Nehru, B., 2018. Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion hippocampus injury in rat brain. Biomed Pharmacother. 97, 458-472.
  • Kato, H., Kuriyama, N., Duarte, S., Clavien, P.A, Busuttil, R.W., Coito, A.J., 2014. MMP-9 deficiency shelters endothelial PECAM-1 expression and enhances regeneration of steatotic livers after ischemia and reperfusion injury. J Hepatol. 60(5), 1032-1039.
  • Leghi, G.E., Domenici, F.A., Vannucchi, H., 2015. Influence of oxıdatıve stress and obesıty ın patıents wıth nonalcoholıc steatohepatıtıs. Arq. Gastroenterol. 52(3), 228-233.
  • Li, X., Liu, J., Lin, L., Wu, J.Q., Li, H.X., Sun, B.J., et.al., 2014. Traditional Chinese medicine shuang shen ning xin attenuates myocardial ischemia/reperfusion injury by preserving of mitochondrial function. Evid. Based Complement Alternat. Med. 2014:180965.
  • Liu, B., Ma, Z.Y., Wu, G., Qian, J.M., 2015. Butyrate protects rats from hepatic ischemia/reperfusion injury. Int. J. Clin. Exp. Med. 8(4), 5406–5413.
  • Mahfoudh-Boussaid, A., Zaouali, M.A., Hauet, T., Hadj-Ayed, K., Miled, A.H., Ghoul-Mazgar, S, et al., 2012. Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment. J. Biomed. Sci. 19 (1), 71.
  • Onay- Besikci, A., Özkan, S.A., 2008. Trimetazidine Revisited: A comprehensive review of the pharmacological effects and analytical techniques for the determination of trimetazidine. Cardiovasc. Ther. 26(2), 147-165.
  • Park, H.S., Jang, J.E., Ko, M.S., Woo, S.H., Kim, B.J., Kim, H.S., et al., 2016. Statins increase mitochondrial and peroxisomal fatty acid oxidation in the liver and prevent non-alcoholic steatohepatitis in mice. Diabetes Metab. J. 40(5), 376-385.
  • Prieto, I., Monsalve, M., 2017. ROS homeostasis, a key determinant in liver ischemic-preconditioning Redox Biol. 12, 1020–1025.
  • Selzner, N., Selzner, M., Jochum, W., Clavien, P.A., 2003. Ischemic preconditioning protects the steatotic mouse liver against reperfusion injury: an ATP dependent mechanism. J Hepatol. 39(1), 55-61.
  • Tao, X., Sun, X., Xu, L., Yin, L., Han, X., Qi, Y., et al., 2016. Total flavonoids from rosa laevigata michx fruit ameliorates hepatic ıschemia/reperfusion injury through inhibition of oxidative stress and inflammation in rats. Nutrients. 8(7), pii E418.
  • Tashiro, H., Kuroda, S., Mikuriya, Y., Ohdan, H., 2014. Ischemia–reperfusion injury in patients with fatty liver and the clinical impact of steatotic liver on hepatic surgery. Surg. Today. 44(9), 1611-1625.
  • Yalçın, A.D., Bisgin, A., Erbay, R.H, Oguz, O., Demir, S., Yilmaz, M., et al., 2012. Trimetazidine effect on burn-induced intestinal mucosal injury and kidney damage in rats. Int. J. Burns Trauma. 2(2), 110-117.
  • Yoo, J.J., Kim, W., Kim, M.Y., Jun, D.W., Kim, S.G., Yeon, J.E., et al., 2019. Recent research trends and updates on nonalcoholic fatty liver disease. Clin. Mol. Hepatol. 25(1), 1-11.
  • Zaouali, M.A., Panisello, A., Lopez, A., Castro, C., Folch, E., Carbonell, T., et al., 2017. GSK3β and VDAC involvement in ER stress and apoptosis modulation during orthotopic liver transplantation. Int. J. Mol. Sci.18(3), 591.
There are 26 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Experimental Research
Authors

Sertaç Ayhan This is me 0000-0002-1915-1306

Tevfik Noyan 0000-0002-7733-0177

Sevil Işık 0000-0002-3535-6977

Sibel Köktürk 0000-0001-5636-3300

Project Number TT-1501
Publication Date April 3, 2021
Submission Date October 1, 2020
Acceptance Date January 6, 2021
Published in Issue Year 2021 Volume: 38 Issue: 2

Cite

APA Ayhan, S., Noyan, T., Işık, S., Köktürk, S. (2021). Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats. Journal of Experimental and Clinical Medicine, 38(2), 66-71.
AMA Ayhan S, Noyan T, Işık S, Köktürk S. Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats. J. Exp. Clin. Med. April 2021;38(2):66-71.
Chicago Ayhan, Sertaç, Tevfik Noyan, Sevil Işık, and Sibel Köktürk. “Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats”. Journal of Experimental and Clinical Medicine 38, no. 2 (April 2021): 66-71.
EndNote Ayhan S, Noyan T, Işık S, Köktürk S (April 1, 2021) Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats. Journal of Experimental and Clinical Medicine 38 2 66–71.
IEEE S. Ayhan, T. Noyan, S. Işık, and S. Köktürk, “Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats”, J. Exp. Clin. Med., vol. 38, no. 2, pp. 66–71, 2021.
ISNAD Ayhan, Sertaç et al. “Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats”. Journal of Experimental and Clinical Medicine 38/2 (April 2021), 66-71.
JAMA Ayhan S, Noyan T, Işık S, Köktürk S. Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats. J. Exp. Clin. Med. 2021;38:66–71.
MLA Ayhan, Sertaç et al. “Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats”. Journal of Experimental and Clinical Medicine, vol. 38, no. 2, 2021, pp. 66-71.
Vancouver Ayhan S, Noyan T, Işık S, Köktürk S. Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats. J. Exp. Clin. Med. 2021;38(2):66-71.