The effect of oral and intraurethral trimetazidine use on urethral healing

Document Type : Original Article


1 Ordu University Medical Faculty, Urology Department, Ordu, Turkey

2 Ordu University Medical Faculty, Clinical Biochemistry Department, Ordu, Turkey

3 Ordu University Medical Faculty, Pathology Department, Ordu, Turkey

4 Ondokuz Mayıs University Medical Faculty, Urology Department, Samsun, Turkey


Objective(s): We aimed to study the effect of trimetazidine (TMZ) on urethral wound repair.
Materials and Methods: A total of 52 male rats were used; 8 groups were formed: 1-week and 3-week control (C1,C3), sham (S1, S3), oral (OT1, OT3), and intraurethral TMZ (IUT1, IUT3) groups. Serum and urine total antioxidant capacity (TAC), total oxidant capacity (TOC), and 8-hydroxy-deoxy-guanosine (8-OHdG) were studied. Hematoxyline-Eosin was used for the histopathological study. In addition, tumor necrosis factor alpha (TNF- α), interleukin 1α, and β levels were compared across groups by an immunohistochemical method.
Results: There were significant differences between C3 and IUT3, OT3 and IUT3 with respect to serum TAC in 3-week groups (P=0.013; P =0.001). Serum TOC levels were significantly different between C3 and IUT3; S3 and OT3; and OT3 and IUT3 groups (P =0.024; P =0.019; P =0.000, respectively). Serum 8-OHdG levels were significantly different between C3 and OT3 groups (P=0.033). In the immunohistochemical examination, C1 and OT1; C1 and IUT1; and S1, S3, OT1, OT3, IUT1 groups were significantly different with respect to IL-1β staining (P=0.007; P =0.000; P=0.009), while there was a significant difference between C3 and S3 with respect to IL-1β (P =0.000).
Conclusion: TMZ increased urinary total oxidant level; while increasing serum TAC levels in the long-term. It also reduced serum TAC levels in urethral use and caused an increase in serum TOC levels with minimal effects on DNA injury and repair. No effect was detected on IL1 α and TNF, but partially reduced the effect on IL-1 β levels.


1. Ayyıldız A, Akgül K.T, Cebeci Ö, Nuhoğlu B, Caydere M, Ustün H, et al. Intraurethral honey application for urethral injury: an experimental study. Int Urol Nephrol 2007; 39: 815-821.
2. Ayyıldız A, Nuhoglu B, Gülerkaya B, Caydere M, Ustün H, Germiyanoglu C, et al. Effect of intraurethral Mitomycin-C on healing and fibrosis in rats with experimentally induced urethral stricture. Int J Urol 2004; 11: 1122-1126.
3. Parihar A, Parihar MS, Milner S, Bhat S. Oxidative stres and antioksidative mobilization in burn injury. Burns 2008; 34: 6-17.
4. Aksoy H, Özakpınar ÖB. Yara iyileşmesi ve  oksidatif stres. Marmara Pharm J 2014; 18: 153-158.
5. Sucu S, Unlu A, Tamer L, Aytacoğlu B, Coskun B, Bilgin R, et al. Effects of trimetazidine on tissue damage in kidney after hindlimb ischemia-reperfusion. Pharmacol Res 2002; 46:345-349.
6. Harpey C, Clauser P, Labrid C, Freyria JL, Poirier JP. Trimetazidine, a cellular anti-ischemic agent. Cardiovasc Drug Rev 1988; 6:292–312.
7. Hauet Th, Bauza G, Goujon M, Caritez JC, Carretier M, Eugene M, et al. Effects of trimetazidine on lipid peroxidation and phosphorous metabolites during cold storage and reperfusion of isolated perfused rat kidney. Pharmacol Exp Ther 1998; 285:1061-1067.
8. Williams FM, Tanda K, Kus M, Williams TJ. Trimetazidine inhibits neutrophil accumulation after myocardial ischemia and reperfusion in rabbits. J Cardiovasc Pharmacol 1993; 22:828-833.
9. Erel O. A novel automated method to measure total antioxidant response againts potent free radical reactions. Clin Biochem 2004; 37:112-119.
10. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38:1103-1111.
11. Ninan N, Thomas S, Grohens Y. Wound healing in urology. Adv Drug Deliv Rev 2015; 82-83:93-105.
12. Kumar S, Wong PF, Leaper DJ. What is new wound healing? Turk J Med Sci 2004; 34:147-160.
13. Yalcinkaya FR, Davarci M, Gokce A, Güven EO, İnci M, Kerem M, et al. Intraurethral utterbasti application for urethral injury in rats. J Anim Vet Adv 2002; 11:1494-1497.
14. Carden DL, Granger DN. Pathophysiology of ischemia-reperfusion injury. J Pathol 2000; 190:255-266.
15. Cross HR. Trimetazidine: a novel protective role via maintenance of Na+-K+ ATPase activity? Cardiovasc Res 2000; 47:637-639.
16. Granger DN. Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol 1988; 255:1269-1275.
17. Wu Q, Qi B, Liu Y. 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.
18. Kuralay F, Çavdar Z. İnflamatuar medyatörlere toplu bakış. Genel Tıp Derg 2006; 16:143-152.
19. Hofer MD, Cheng EY, Bury MI, Park E, Xu W, Hong SJ, et al. Analysis of primary urethral wound healing in the rat. Urology 2014; 84:246. e241-e247