Ali AYYILDIZ, Rüştü Cankon GERMİYANOĞLU, Erdal BENLİ, Abdullah ÇIRAKOĞLU, Tevfik NOYAN, Sema Nur AYYILDIZ, Selma CIRRIK

The effect of trimetazidine on renal oxidative stress in partial and complete ureteral obstructions in a rat model

Background/aim: Renal oxidative stress occurs in ureteral obstructions. The purpose of this study was to investigate the effect of the antioxidant and antiischemic agent trimetazidine (TMZ) on oxidative stress following ureteral obstruction. Materials and methods: Ten groups were established. Sham groups were checked as controls after 1 and 3 weeks. The other 8 groups had partial or complete ureteral obstruction while receiving or not receiving trimetazidine (TMZ) at 5 mg/kg daily and were evaluated after either 1 week or 3 weeks. Creatinine and cystatin C measurements were performed in the serum. Malondialdehyde, myeloperoxidase, catalase, and glutathione peroxidase activity were measured in renal tissue and serum. Results: In the 1-week groups, tissue malondialdehyde, serum myeloperoxidase, and glutathione peroxidase activity increased significantly with obstruction and TMZ use compared to the control group (P < 0.005). In the 3-week TMZ group, cystatin C, tissue malondialdehyde, serum and tissue myeloperoxidase, and tissue glutathione peroxidase differed significantly (P < 0.05). There was no significant difference in all parameters after 3 weeks of partial obstruction (P > 0.05), with only serum malondialdehyde being significantly elevated (P < 0.05). Conclusion: TMZ did not exhibit a renal oxidative stress-lowering effect in obstruction. It causes mild impairment of renal functions in obstruction. Patients using TMZ must be closely monitored in terms of kidney function in the event of any ureteral obstruction.

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1. Gulmi FA, Felsen D. Üriner sistem obstrüksiyonunun patofizyolojisi (Çev. Sarıkaya Ş). In: Yaman Ö, editor. Campbell Üroloji (Türkçe Çeviri). 8th ed. Ankara, Turkey: Güneş Kitabevi; 2005. pp. 411-462 (in Turkish).
2. Singh D, Kaur R, Chander V, Chopra K. Antioxidants in the prevention of renal disease. J Med Food 2006; 9: 443-450.
3. Alfadda AA, Sallam RM. Reactive oxygen species in health and disease. J Biomed Biotechnol 2012; 2012: 936486.
4. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organization Journal 2012; 5: 9-19.
5. Kayış T. Diazinonun subletal konsantrasyonlarının Pimplaturionellae L.nin eşey oranı ve bazı biyokimyasal parametreleri üzerine etkileri. PhD, Çukurova University, Adana, Turkey, 2010 (in Turkish).
6. Banerjee M, Vats P. Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus. Redox Biol 2014; 2: 170-177.
7. Reyes JL, Molina-Jijón E, Rodríguez-Muñoz R, Bautista-García P, Debray-García Y, Namorado MC. Tight junction proteins and oxidative stress in heavy metals-induced nephrotoxicity. Biomed Research International 2013; 2013: 730789.
8. Chevalier RL, Forbes MS, Thornhill BA. Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int 2009; 75: 1145-1152.
9. Dendooven A, Ishola DA Jr, Nguyen TQ, Van der Giezen DM, Kok RJ, Goldschmeding R, Joles JA. Oxidative stress in obstructive nephropathy. Int J Exp Pathol 2011; 92: 202-210.
10. Kantor P, Lucien A, Kozak R, Lopaschuk GD. The anginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86: 580-588.
11. Pekcetin C, Ergur BU, Kiray M, Bagriyanik A, Tugyan K, Erbil G, Ozogul C. The protective effects of trimetazidine on testicular ischemia and reperfusion injury in rats. Pediatr Surg Int 2007; 23: 1113-1118.
12. Satyanarayana PS, Chopra K. Oxidative stress-mediated renal dysfunction by cyclosporine A in rats: attenuation by trimetazidine. Renal Failure 2002; 24: 259-274.
13. Lopes RI, Denes FT, Bartolamei MG, Reis S, Sanches TR, Leite KR, Srougi M, Seguro AC. Serum and urinary values of CA 19-9 and TGFβ1 in a rat model of partial or complete ureteral obstruction. Eur J Pediatr Surg 2015; 25: 513-519.
14. Kinter M, Wolstenholme JT, Thornhill BA, Newton EA, McCormick ML, Chevalier RL. Unilateral ureteral obstruction impairs renal antioxidant enzyme activation during sodium depletion. Kidney Int 1999; 55: 1327-1334.
15. Tang J, Jiang X, Zhou Y, Xia B, Dai Y. Increased adenosine levels contribute to ischemic kidney fibrosis in the unilateral obstruction model. Exp Ther Med 2015; 9: 737-743.
16. Wu Q, Qi B, Liu Y, Cheng B, Liu L, Li Y, Wang Q. Mechanisms underlying protective effects of trimetazidine on endothelial progenitor cells biological functions against H2O2-induced injury: involvement of antioxidation and Akt/eNOS signaling pathways. Eur J Pharmacol 2013; 707: 87-94.
17. Hassanzadeh G, Hosseini A, Pasbakhsh, Akbari M, Ghaffarpour M, Takzare N, Zahmatkesh M. Trimetazidine prevents oxidative changes induced in a rat model of sporadic type of Alzheimers disease. Acta Medica Iran 2015; 53: 17-24.
18. Yalcin AD, Bisgin A, Erbay RH, Oguz O, Demir S, Yilmaz M, Gumuslu S. Trimetazidine effect on burn-induced intestinal mucosal injury and kidney damage in rats. International Journal of Burns and Trauma 2012; 2: 110-117.
19. Marnett LJ. Lipid peroxidation-DNA damage by malondialdehyde. Mutat Res 1999; 424: 83-95.
20. Miyamoto S, Almeida EA, Nogueira L, Medeiros MHG, Mascio PD. Evaluation of malondialdehyde levels. In: Abele D, Zentano-Savin T, Vasquez-Medina JP, editors. Oxidative Stress in Aquatic Ecosystems. Hoboken, NJ, USA: John Wiley & Sons; 2011. pp. 440-447.
21. Tirani SA, Pezeshki Z, Nematbakhsh M, Nasri H, Talebi A. Effect of L-arginine and L-NAME on kidney tissue damage in rats after 24 h of bilateral ureteral obstruction. International Journal of Preventive Medicine 2015; 6: 60.
22. Pulli B, Ali M, Forghani R, Schob S, Hsieh KLC, Wojtkiewicz G, Linnoila JJ, Chen JW. Measuring myeloperoxidase activity in biological samples. PLoS ONE 2013; 8: e67976.
23. Chevrier I, Tregouet DA, Masonnet-Castel S, Beaune P, Loriot MA. Myeloperoxidase genetic polymorphisms modulate human neutrophil enzyme activity: genetic determinants for atherosclerosis. Atherosclerosis 2006; 188: 150-154.
24. Piedrafita FJ, Molander RB, Vansant G, Orlova EA, Pfahl M, Reynolds WF. An Alu element in the myeloperoxidase promoter contains a composite SPI-thyroid hormone-retinoic acid response element. J Biol Chem 1996; 271: 14412-14420.