Investigation of tyrphostin AG 556 for testicular torsion-induced ischemia reperfusion injury in rat

J Pediatr Urol. 2014 Apr;10(2):223-9. doi: 10.1016/j.jpurol.2013.08.007. Epub 2013 Sep 11.


Objective: To investigate the effects of tyrphostin AG 556, a tyrosine kinase inhibitor (TKI) in an experimental model of testicular ischemia-reperfusion (I/R) injury.

Material and methods: Twenty-four adult male rats were randomly divided into four groups (n = 6): sham, torsion/detorsion (T/D), T/D + dimethylsulfoxide (DMSO) (vehicle group), and T/D + DMSO + tyrphostin AG 556. Testicular torsion was achieved by rotating the left testis 720° clockwise for 4 h. Thirty minutes before detorsion, 3 mg/kg tyrphostin AG 556 was injected transperitoneally in the AG 556 group and DMSO was injected transperitoneally in the DMSO group. After 2 h of reperfusion arterial blood samples were collected for biochemical analysis for malondialdehyde (MDA), ischemia modified albumin (IMA), SCUBE1 (signal peptide-CUB [complement C1r/C1s, Uegf, and Bmp1] and EGF [epidermal growth factor] like domain-containing protein 1), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) parameters, and ipsilateral orchiectomies were performed for histopathological examination based on the semi-quantitative Johnsen's mean testicular biopsy score (MTBS) in all groups.

Results: Tyrphostin AG 556 exhibited a protective effect against I/R injury in testicular torsion. Of the biochemical parameters evaluated as a result of testicular I/R, IMA, MDA, and TOS levels were significantly elevated. There was no significant difference in terms of these biochemical parameters between the sham and AG 556 groups. Significant histopathological injury was determined by comparing the T/D and sham groups. According to histopathological injury scores, significant differences were determined between T/D and AG 556 groups and between AG 556 and sham groups. AG 556 had a superior improving effect on Johnsen's scores than DMSO.

Conclusions: Our results suggest that the use of tyrphostin AG 556 prior to testicular reperfusion has a protective effect against testicular I/R injury.

Keywords: Ischemia reperfusion injury; Rat; Testicular torsion; Tyrphostin Ag 556.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biopsy, Needle
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology
  • Spermatic Cord Torsion / complications
  • Spermatic Cord Torsion / drug therapy*
  • Spermatic Cord Torsion / pathology
  • Treatment Outcome
  • Tyrphostins / pharmacology*


  • Tyrphostins
  • AG 556
  • Malondialdehyde