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Effects of polydeoxyribonucleotide on the histological damage and the altered spermatogenesis induced by testicular ischaemia and reperfusion in rats.

Abstract
The effects of polydeoxyribonucleotide (PDRN), an agonist of the A2A adenosine receptors which when activated positively influences sperm activity, were tested in an experimental testicular ischaemia/reperfusion injury model. Anaesthetized male Sprague-Dawley rats were subjected to testicular torsion-induced ischaemia, followed by reperfusion (TI/R). Immediately after detorsion, randomized animals, including SHAM, received intraperitoneal injections of: (i) vehicle (1 mL/kg 0.9% NaCl solution); (ii) PDRN (8 mg/kg); (iii) DMPX (3,7-dimethyl-1-propargilxanthine, 0.1 mg/kg); or (iv) PDRN (8 mg/kg) + DMPX (0.1 mg/kg). Animals were euthanized at 1, 7 and 30 days following reperfusion. Vascular endothelial growth factor (VEGF) expression is normally associated with adenosine A2A receptor stimulation. After treatment, VEGF mRNA/protein expression quantified by qPCR and Western blot, vascular endothelial growth factor receptor-1 (VEGFR1) and endothelial nitric oxide synthase (eNOS) mRNA measured by qPCR, VEGF and VEGFR1 assessed using immunohistochemical methods, histological staining and spermatogenic activity were all analysed. Testis ischaemia-reperfusion (TI/R) injury caused increases in VEGF mRNA and protein, VEGFR1 and eNOS mRNA, histological damage and reduced spermatogenic activity. Immunostaining showed a lower expression of VEGF in germinal epithelial cells and a strong expression of VEGFR1 in Leydig cells after TI/R. PDRN administration increased significantly VEGF message/protein, VEGFR1 and eNOS message, decreased histological damage and ameliorated spermatogenic activity. PDRN might be useful in the management of testicular torsion.
AuthorsL Minutoli, P Antonuccio, F Squadrito, A Bitto, P A Nicotina, C Fazzari, F Polito, H Marini, G Bonvissuto, S Arena, G Morgia, C Romeo, A P Caputi, D Altavilla
JournalInternational journal of andrology (Int J Androl) Vol. 35 Issue 2 Pg. 133-44 (Apr 2012) ISSN: 1365-2605 [Electronic] England
PMID21651579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.
Chemical References
  • Adenosine A2 Receptor Agonists
  • Polydeoxyribonucleotides
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide Synthase Type III
  • Vascular Endothelial Growth Factor Receptor-1
Topics
  • Adenosine A2 Receptor Agonists (pharmacology)
  • Animals
  • Immunohistochemistry
  • Leydig Cells (metabolism)
  • Male
  • Nitric Oxide Synthase Type III (genetics, metabolism)
  • Polydeoxyribonucleotides (pharmacology)
  • RNA, Messenger (genetics, metabolism)
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (drug therapy, metabolism, pathology)
  • Spermatic Cord Torsion (drug therapy, metabolism, pathology)
  • Spermatogenesis (drug effects)
  • Testis (blood supply, drug effects, pathology)
  • Vascular Endothelial Growth Factor A (genetics, metabolism)
  • Vascular Endothelial Growth Factor Receptor-1 (biosynthesis, genetics, metabolism)

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