title: 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.
authors.affiliation: Section of Pharmacology, Department of Experimental and Clinical Medicine and Pharmacology, University of Messina, Messina, Italy. lminutoli@unime.it
authors.forename: L
authors.initials: L
authors.lastname: Minutoli
authors.forename: P
authors.initials: P
authors.lastname: Antonuccio
authors.forename: F
authors.initials: F
authors.lastname: Squadrito
authors.forename: A
authors.initials: A
authors.lastname: Bitto
authors.forename: P A
authors.initials: PA
authors.lastname: Nicotina
authors.forename: C
authors.initials: C
authors.lastname: Fazzari
authors.forename: F
authors.initials: F
authors.lastname: Polito
authors.forename: H
authors.initials: H
authors.lastname: Marini
authors.forename: G
authors.initials: G
authors.lastname: Bonvissuto
authors.forename: S
authors.initials: S
authors.lastname: Arena
authors.forename: G
authors.initials: G
authors.lastname: Morgia
authors.forename: C
authors.initials: C
authors.lastname: Romeo
authors.forename: A P
authors.initials: AP
authors.lastname: Caputi
authors.forename: D
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013086:Spermatic Cord Torsion / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D011089:Polydeoxyribonucleotides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D040281:Vascular Endothelial Growth Factor Receptor-1