{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:56:49Z","timestamp":1781672209378,"version":"3.54.5"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Testicular torsion (TT) induces ischemia\u2013reperfusion (I\/R) damage, frequently resulting in inflammatory responses, oxidative stress, and compromised spermatogenesis. This study investigated the potential therapeutic role of theophylline\u2014a methylxanthine with established antioxidant and anti-inflammatory properties\u2014on testicular I\/R outcomes in a rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-two pubertal Wistar\u2013Albino rats were categorized into four cohorts (n=8 per group): Control, I\/R, and I\/R treated with either 10 mg\/kg or 50 mg\/kg theophylline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>While plasma biochemical markers (tumor necrosis factor-alpha (TNF-\u03b1), glutathione, myeloperoxidase, ischemia-modified albumin, inhibin B, caspase-3, and testosterone) and histopathological Johnsen tubular biopsy scores remained statistically comparable across groups, significant intergroup variations were observed in testicular tissue TNF-\u03b1 (p = 0.017), testicular testosterone (p = 0.003), and Cosentino histopathological grades (p &amp;lt; 0.05).Although high-dose theophylline showed a downward trend in tissue TNF-\u03b1, this specific pairwise difference did not reach statistical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results indicate that while acute structural protection was limited within a 4-hour reperfusion window, high-dose theophylline demonstrates a promising capacity to preserve testicular testosterone levels and modulate local inflammatory markers. This suggests a dose-dependent supportive effect on Leydig cell function and endocrine recovery following ischemic insult.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1814726","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:43:58Z","timestamp":1781671438000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-dependent protective effects of theophylline on testicular endocrine function in a rat model of ischemia-reperfusion injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Duygu","family":"Demiriz Gulmez","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Reanimation, University of Health Sciences Ba\u015fak\u015fehir \u00c7am and Sakura City Hospital","place":["Istanbul, T\u00fcrkiye"]},{"name":"Department of Anesthesiology and Reanimation, Giresun University School of Medicine","place":["Giresun, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alparslan","family":"Apan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Giresun University School of Medicine","place":["Giresun, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozgun","family":"Cuvas Apan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Giresun University School of Medicine","place":["Giresun, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Usta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Giresun University School of Medicine","place":["Giresun, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esma","family":"Cinar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Giresun University School of Medicine","place":["Giresun, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e13716","DOI":"10.1111\/and.13716","article-title":"Protective effects of royal jelly on testicular torsion induced ischaemia reperfusion injury in rats","volume":"52","author":"Abbaszadeh","year":"2020","journal-title":"Andrologia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.jpedsurg.2019.09.028","article-title":"The long term effects of intrascrotal low dose and high dose N-acetylcysteine on testis damage in rat model of testicular torsion","volume":"55","author":"Acer-Demir","year":"2020","journal-title":"J. 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