Ethyl pyruvate reduces germ cell-specific apoptosis and oxidative stress in rat model of testicular torsion/detorsion

J Pediatr Surg. 2008 Apr;43(4):705-12. doi: 10.1016/j.jpedsurg.2007.12.063.

Abstract

Purpose: Testicular torsion/detorsion (T/D) results in enhanced formation of free radical metabolites, which contributes to the pathophysiology of tissue damage. We investigated the protective effects of ethyl pyruvate (EP) against testis tissue damage in an experimental model of testicular torsion.

Methods: Sprague-Dawley rats were divided into 5 groups. In those animals that underwent T/D, right testes were rotated 720 degrees for 1 hour. Group 1 control rats underwent sham operation. In group 2, the rats underwent T/D. The EP was prepared and injected in the form of Ringer's ethyl pyruvate solution. The rats in group 3, 4, and 5 received 2 doses of 20, 50, and 100 mg/kg EP (30 minutes before and after detorsion), respectively. The right testes of 6 animals from each group were excised 4 hours after detorsion for the measurement of lipid peroxidation, myeloperoxidase (MPO), and antioxidant enzymes activities. Germ cell apoptosis was determined in right testes of 8 animals per group 24 hours after detorsion. The epididymal sperm concentration and motility were evaluated 1 month after treatments.

Results: Germ cell apoptosis indices were significantly higher in group 2 compared with control group. The level of lipid peroxidation and MPO activity increased, whereas antioxidant enzymes activities decreased after T/D. Sperm count and motility were also reduced 1 month after T/D in group 2 rats. However, EP treatment at doses of 50 and 100 mg/kg significantly decreased the early apoptotic damage and improved long-term sperm count and motility. In the same dosing groups, we observed normalization of oxidant/antioxidant balance and decrement of MPO activity. However, administration of 20 mg/kg of EP conferred no protective effect.

Conclusions: Administration of Ringer's ethyl pyruvate solution (in appropriate doses) is protective against apoptotic tissue damage following testicular torsion and improves long-term testicular function. The antioxidant and anti-inflammatory properties of EP seem responsible for the protective effects. Our findings suggest this resuscitation solution as a possible substitute for fluid and electrolyte maintenance during surgical detorsion.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Dose-Response Relationship, Drug
  • Germ Cells
  • Ischemia / drug therapy
  • Ischemia / etiology
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidative Stress / drug effects*
  • Peroxidase / metabolism
  • Postoperative Care
  • Pyruvates / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sperm Count
  • Sperm Motility
  • Spermatic Cord Torsion / complications
  • Spermatic Cord Torsion / physiopathology*
  • Spermatic Cord Torsion / surgery
  • Testis / physiopathology

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Pyruvates
  • ethyl pyruvate
  • Peroxidase