{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:47:41Z","timestamp":1788821261051,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Polydeoxyribonucleotide (PDRN) is an agonist of the A2A adenosine receptor derived from salmon trout sperm. Selenium (Se) is a trace element normally present in the diet. We aimed to investigate the long-term role of PDRN and Se, alone or in association, after ischemia-reperfusion (I\/R) in rats. The animals underwent 1 h testicular ischemia followed by 30 days of reperfusion or a sham I\/R and were treated with PDRN or Se alone or in association for 30 days. I\/R significantly increased hypoxia-inducible factor 1-\u03b1 (HIF-1\u03b1) in Leydig cells, malondialdehyde (MDA), phosphorylated extracellular signal-regulated kinases 1\/2 (pErk 1\/2), and apoptosis decreased testis weight, glutathione (GSH), testosterone, nuclear factor erythroid 2-related factor 2 (Nrf2), induced testicular structural changes, and eliminated HIF-1\u03b1 spermatozoa positivity. The treatment with either PDRN or Se significantly decreased MDA, apoptosis, and HIF-1\u03b1 positivity of Leydig cells, increased testis weight, GSH, testosterone, and Nrf2, and improved the structural organization of the testes. PDRN and Se association showed a higher protective effect on all biochemical, structural, and immunohistochemical parameters. Our data suggest that HIF-1\u03b1 could play important roles in late testis I\/R and that this transcriptional factor could be modulated by PDRN and Se association, which, together with surgery, could be considered a tool to improve varicocele-induced damages.<\/jats:p>","DOI":"10.3390\/ijms232113144","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"13144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Involvement of Hypoxia-Inducible Factor 1-\u03b1 in Experimental Testicular Ischemia and Reperfusion: Effects of Polydeoxyribonucleotide and Selenium"],"prefix":"10.3390","volume":"23","author":[{"given":"Pietro","family":"Antonuccio","sequence":"first","affiliation":[{"name":"Department of Human Adult and Childhood Pathology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-2265","authenticated-orcid":false,"given":"Giovanni","family":"Pallio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8254-177X","authenticated-orcid":false,"given":"Herbert Ryan","family":"Marini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1134-7080","authenticated-orcid":false,"given":"Natasha","family":"Irrera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7616-5480","authenticated-orcid":false,"given":"Carmelo","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Human Adult and Childhood Pathology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Puzzolo","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Freni","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Pirrotta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8868-0762","authenticated-orcid":false,"given":"Francesco","family":"Squadrito","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letteria","family":"Minutoli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Micali","sequence":"additional","affiliation":[{"name":"Department of Human Adult and Childhood Pathology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.prp.2013.04.002","article-title":"Testicular and paratesticular pathology in the pediatric population: A 20 year experience at Riley hospital for children","volume":"209","author":"Fan","year":"2013","journal-title":"Pathol. 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