Inhibition of poly(adenosine diphosphate-ribose) polymerase decreases long-term histologic damage in testicular ischemia-reperfusion injury

Urology. 2004 Apr;63(4):791-5. doi: 10.1016/j.urology.2003.10.062.

Abstract

Objectives: To evaluate the effect of 3-aminobenzamide, an inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), on the long-term histologic damage in testicular ischemia-reperfusion injury. PARP inhibitors have been used successfully to decrease ischemia-reperfusion injury in several organ systems.

Methods: Adult male Wistar rats were divided into four groups of 7 rats each. One group underwent 2 hours of testicular torsion; one received pretreatment with vehicle (dimethyl sulfoxide) before detorsion; one received pretreatment with 3-aminobenzamide, an inhibitor of PARP, before detorsion; and one group underwent a sham operation. All rats underwent bilateral orchiectomy 60 days after the experiment. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histologic examination of each testis.

Results: Testicular torsion-detorsion caused a significant decrease in the mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score in the ipsilateral testes (P <0.001), but not in the contralateral testes. The animals treated with 3-aminobenzamide had a statistically significant increase in these histologic parameters compared with the torsion-detorsion group (P <0.01).

Conclusions: The results of this study show that PARP may have a role in the testicular damage caused by ischemia-reperfusion. Administering PARP inhibitors before reperfusion may have the potential to decrease the long-term histologic damage that occurs after testicular torsion.

MeSH terms

  • Animals
  • Benzamides / pharmacology*
  • Benzamides / therapeutic use
  • Biopsy
  • Dimethyl Sulfoxide / pharmacology
  • Dimethyl Sulfoxide / therapeutic use
  • Disease Models, Animal
  • Humans
  • Male
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / pathology*
  • Reperfusion Injury / prevention & control*
  • Seminiferous Tubules / blood supply
  • Seminiferous Tubules / drug effects
  • Seminiferous Tubules / pathology
  • Spermatic Cord Torsion / drug therapy*
  • Spermatic Cord Torsion / pathology*
  • Testis / blood supply*
  • Testis / drug effects
  • Testis / pathology*
  • Treatment Outcome

Substances

  • Benzamides
  • Poly(ADP-ribose) Polymerase Inhibitors
  • 3-aminobenzamide
  • Dimethyl Sulfoxide