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01-11-2007 | Original Article

The protective effects of trimetazidine on testicular ischemia and reperfusion injury in rats

Authors: Cetin Pekcetin, Bekir Ugur Ergur, Muge Kiray, Alper Bagriyanik, Kazim Tugyan, Guven Erbil, Candan Ozogul

Published in: Pediatric Surgery International | Issue 11/2007

Abstract

This study was designed to investigate the protective effect of trimetazidine [TMZ; 1-(2, 3, 4-trimethhoxibenzyl)-piperazine dihydrochloride], as an antioxidant agent, on torsion–detorsion-induced biochemical and histopathological changes in experimental testicular ischemia/reperfusion injury in rats. Twenty-seven male Wistar rats weighing 180–220 g were divided into five groups: control (C, n = 4), sham-operated (S, n = 4), ischemia (I, n = 6), ischemia–reperfusion (I/R, n = 6) and ischemia–reperfusion + trimetazidine (I/R + TMZ; n = 7). Control rats were used for basal normal values. In group I, 2 h torsion of the left testis was performed. In I/R and I/R + TMZ groups, following 2 h of torsion, 4 h detorsion of the testis was performed. In ischemia and I/R groups, physiologic saline was administered orally for 7 days, and the rats in I/R + TMZ group were pretreated orally with 5 mg/kg day TMZ for 7 days before inducing ischemia. At the end of each experiment, ipsilateral orchiectomies were performed for the tissue levels of malondialdehyde (MDA), glutathione peroxidase (GPx) enzyme activities and histopathological examinations in all groups. MDA levels were significantly reduced and GPx enzyme activities were significantly increased in testes in I/R+TMZ pretreated group compared to group I and I/R. The mean seminiferous tubular diameter (MSTD) and Johnsen’s score were significantly better in I/R+TMZ group than groups I and I/R. Pretreatment with TMZ decreased germ cell apoptosis and caspase-3 expression in the ischemic testis.

The present results show that TMZ has a protective activity in the testicular injury caused by I/R, and provide the first evidence of the role of TMZ for the prevention of I/R-induced testicular injury.

Cuckow PM, Frank JD (2000) Torsion of the testis. BJU Int 86: 349–353PubMedCrossRef

Etensel B, Ozkısacık S, Ozkara E, Karul A, Oztan O, Yazıcı M, Gursoy H (2007) Dexpanthenol attenuates lipid peroxidation and testicular damage at experimental ischemia and reperfusion injury. Pediatr Surg Int 23:177–181PubMedCrossRef

Power RE, Scanlon R, Kay EW, Creagh TA, Bouchier-Hayes DJ (2003) Long-term protective effects of hypothermia on reperfusion injury post-testicular torsion. Scand J Urol Nephrol 37:456–460PubMedCrossRef

Cay A, Alver A, Kucuk M, Isik O, Eminagaoglu MS, Karahan SC, Deger O (2006) The effects of N-acetylcysteine on antioxidant enzyme activities in experimental testicular torsion. J Surg Res 131(2):199–203PubMedCrossRef

Mogilner JG, Elenberg Y, Lurie M, Shiloni E, Coran AG, Sukhotnik I (2006) Effect of dexamethasone on germ cell apoptosis in the contralateral testis after testicular ischemia–reperfusion injury in the rat. Fertil Steril 85(Suppl 1):1111–1117PubMedCrossRef

Turner TT, Tung KSK, Tomomasa H, Wilson LW (1997) Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol Reprod 57:1267–1274PubMedCrossRef

Turner TT, Bang HJ, Lysiak JL (2004) The molecular pathology of experimental testicular torsion suggests adjunct therapy to surgical repair. J Urol 172:2574–2578PubMedCrossRef

Ikizler M, Erkasap N, Dernek S, Batmaz B, Kural T, Kaygisiz Z (2006) Trimetazidine-induced enhancement of myocardial recovery during reperfusion: a comparative study in diabetic and non-diabetic rat hearts. Arch Med Res 37(6):700–708PubMedCrossRef

Yukselen V, Karaoglu AO, Yenisey C, Tuncyurek M, Ozutemiz O (2005) Trimetazidine reduces the degree of fibrosis in alkali burns of the esophagus. J Pediatr Surg 40(3):505–509PubMedCrossRef

10.

Singh D, Chopra K (2004) Effect of trimetazidine on renal ischemia/reperfusion injury in rats. Pharmacol Res 50(6):623–629PubMedCrossRef

11.

Inci I, Dutly A, Inci D, Boehler A, Weder W (2001) Recipient treatment with trimetazidine improves graft function and protects energy status after lung transplantation. J Heart Lung Transplant 20(10):1115–1122PubMedCrossRef

12.

Mohand-Said S, Jacquet A, Lucien A, Espinasse-Berrod MA, Frasson Correa De Silva M, Sahel J (2002) Protective effect of trimetazidine in a model of ischemia–reperfusion in the rat retina. Ophthalmic Res 34(5):300–305PubMedCrossRef

13.

Baltalarli A, Coskun E, Ortac R, Onem G, Goksin I, Sirin BH (2000) Protective effects of trimetazidine in transient spinal cord ischemia. Res Exp Med (Berl) 200(1):43–51

14.

Johnsen SG (1970) Testicular biopsy score count-a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1(1):2–25PubMedCrossRef

15.

Filho DW, Torres MA, Bordin ALB, Crezcynski-Pasa TB, Boveris A (2004) Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia–reperfusion injury. Mol Aspects Med 25(1–2):199–210PubMedCrossRef

16.

Turner TT, Brown KJ (1993) Spermatic cord torsion: loss of spermatogenesis despite return of blood flow. Biol Reprod 49(2):401–407PubMedCrossRef

17.

Gezici A, Ozturk H, Buyukbayram H, Ozturk H, Okur H (2006) Effects of gabexate mesilate on ischemia–reperfusion-induced testicular injury in rats. Pediatr Surg Int 22(5):435–441PubMedCrossRef

18.

Salmasi AH, Beheshtian A, Payabvash S, Demehri S, Ebrahimkhani MR, Karimzadegan M, Bahadori M, Pasalar P, Dehpour AR (2005) Effect of morphine on ischemia–reperfusion injury: experimental study in testicular torsion rat model. Urology 66(6):1338–1342PubMedCrossRef

19.

Iskesen I, Saribulbul O, Cerrahoglu M, Var A, Nazli Y, Sirin H (2006) Trimetazidine reduces oxidative stress in cardiac surgery. Circ J 70(9):1169–1173PubMedCrossRef

20.

Inci I, Dutly A, Rousson V, Boehler A, Weder W (2001) Trimetazidine protects the energy status after ischemia and reduces reperfusion injury in a rat single lung transplant model. J Thorac Cardiovasc Surg 122(6):1155–1161PubMedCrossRef

21.

Tetik C, Ozden A, Calli N, Bilgihan A, Bostanci B, Yis O, Bayramoglu H (1999) Cytoprotective effect of trimetazidine on 60 minutes of intestinal ischemia–reperfusion injury in rats. Transpl Int 12(2):108–112PubMedCrossRef

22.

Tunckiran A, Cayan S, Bozlu M, Yilmaz N, Acar D, Akbay E (2005) Protective effect of vascular endothelial growth factor on histologic changes in testicular ischemia–reperfusion injury. Fertil Steril 84(2):468–473PubMedCrossRef

23.

Argaud L, Gomez L, Gateau-Roesch O, Couture-Lepetit E, Loufouat J, Robert D, Ovize M (2005) Trimetazidine inhibits mitochondrial permeability transition pore opening and prevents lethal ischemia–reperfusion injury. J Mol Cell Cardiol 39(6):893–899PubMedCrossRef

Title: The protective effects of trimetazidine on testicular ischemia and reperfusion injury in rats
Authors: Cetin Pekcetin
Bekir Ugur Ergur
Muge Kiray
Alper Bagriyanik
Kazim Tugyan
Guven Erbil
Candan Ozogul
Publication date: 01-11-2007
Publisher: Springer-Verlag
Published in: Pediatric Surgery International / Issue 11/2007
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-007-2002-y

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The protective effects of trimetazidine on testicular ischemia and reperfusion injury in rats

Abstract

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Abstract

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