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Ischaemic post-conditioning (IPostC) might represent an innovative surgical approach to protect organs from ischaemia and reperfusion (I/R) injury. We investigated the molecular mechanisms underlying the contrasting effects of IPostC on the early and late damage induced by testicular I/R injury. Testis I/R was induced by occluding the right testicular vessels using a clip. Male rats were divided into the following groups: sham, I/R and I/R + IPostC. In the I/R group, the clip was removed after 60 min of ischaemia, and reperfusion was allowed for 30 min, 1 and 30 days. In the I/R + IPostC group, three cycles of 30-sec reperfusion and 30-sec ischaemia were performed after 60 min of ischaemia and then reperfusion followed up for 30 min, 1 and 30 days. Following 30-min reperfusion, there was an increase in mitogen-activated protein kinases (MAPKs) in I/R rats; after 1 day of reperfusion, interleukin-6, tumour necrosis factor-α and nuclear factor-κB (NF-κB) expression were significantly increased; IκB-α expression reduced; and a marked damage in both testes was observed. IPostC inhibited MAPKs, cytokines and NF-κB expression, augmented IκB-α expression and decreased histological damage in testes subjected to I/R. After 30 days of reperfusion, I/R injury activated the apoptosis machinery, caused severe histological damage and reduced spermatogenic activity. By contrast, IPostC did not modify the apoptotic markers, the histological alterations as well as spermatogenic activity following 30 days of reperfusion. Our data demonstrate that IPostC protects the testis from the early damage induced by I/R injury, but it does not protect against the late damage., (© 2013 American Society of Andrology and European Academy of Andrology.)

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., (© 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.)

Purpose: Testicular torsion is a medical emergency that requires immediate diagnosis and treatment to avoid subsequent testicular injury and infertility. PPARs are a family of nuclear hormone receptors belonging to the steroid receptor superfamily. Three PPAR isotypes (α, β/δ and γ) encoded by separate genes and showing different tissue distribution patterns have been identified. PPARβ/δ is expressed in testis and its role is largely unknown. We tested whether pharmacological activation of PPARβ/δ might protect the testis from ischemia and reperfusion injury. Materials and Methods: Adult male Sprague-Dawley rats were subjected to 1-hour testicular ischemia, followed by 24 hours of reperfusion. Sham testicular ischemia-reperfusion rats served as controls. The animals were randomized to receive immediately after detorsion 1) L-165,041 (4 mg/kg intraperitoneally), a potent agonist of PPARβ/δ, 2) GW9662 (Calbiochem®) (4 mg/kg intraperitoneally), an antagonist of PPAR, 3) L-165,041 (4 mg/kg intraperitoneally) plus GW9662 (4 mg/kg intraperitoneally) concomitantly or 4) vehicle (1 ml/kg 10% dimethyl sulfoxide/NaCl solution). We evaluated testicular extracellular signal regulated kinase, tumor necrosis factor-α and interleukin-6 by Western blot. We also investigated PPARβ/δ activation by Western blot, mRNA expression and organ damage. Results: Testicular ischemia-reperfusion injury caused a significant increase in extracellular signal regulated kinase, tumor necrosis factor-α and interleukin-6 expression in each testis. Furthermore, histological examination revealed marked damage. L-165,041 administration increased the PPARβ/δ message and protein, inhibited extracellular signal regulated kinase, tumor necrosis factor-α and interleukin-6 expression, and decreased histological damage. Concomitant administration of GW9662 reversed the protection exerted by PPARβ/δ agonist. Conclusions: These findings indicate that PPARβ/δ agonists might be an attractive therapeutic candidate for managing testicular torsion. [Copyright &y& Elsevier]