{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:11:13Z","timestamp":1792548673433,"version":"4.5.0"},"reference-count":90,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia","award":["0010-1446-S"],"award-info":[{"award-number":["0010-1446-S"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes mellitus (DM) is recognized as a major contributor to impaired testicular function and compromised male fertility. In the present study, the protective effects of the natural flavonoid diosmin (Dios) against diabetes-induced testicular injury were investigated using a rat model of streptozotocin (STZ)-induced diabetes. Diabetes was induced in rats via a single intraperitoneal injection of STZ at a dose of 50 mg\/kg body weight. Dios was administered at doses of 25 and 50 mg\/kg body weight for eight weeks. Diabetic rats displayed marked testicular dysfunction, evidenced by reduced serum testosterone levels, deteriorated sperm parameters, and pronounced histopathological alterations in testicular tissues. Biochemical analysis revealed elevated levels of oxidative stress markers, including malondialdehyde and protein carbonyls, along with decreased levels of reduced glutathione and diminished activities of catalase and superoxide dismutase in the testicular tissues. Furthermore, diabetes exacerbated testicular inflammation, as indicated by increased immunoexpression of NF-\u03baB p65 and levels of pro-inflammatory cytokines. Likewise, diabetes induced testicular apoptosis, demonstrated by increased Bax and caspase-3 levels and decreased Bcl-2 levels. Treatment of diabetic rats with Dios significantly attenuated sperm parameters and testicular architecture and mitigated oxidative stress, inflammatory responses, and apoptotic cell death. Additionally, Dios enhanced antioxidant defense mechanisms and restored the Sirt1\/Nrf2\/HO-1 signaling pathway in the testicular tissues of diabetic rats. These results suggest that Dios may serve as an adjuvant therapeutic agent for diabetes-associated testicular dysfunction.<\/jats:p>","DOI":"10.3390\/ijms27031268","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"1268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Modulation of Oxidative Stress, Inflammation, and Apoptosis and Restoration of Sirt1\/Nrf2\/HO-1 Signaling by Diosmin Protect Against Diabetes-Induced Testicular Damage in Rats"],"prefix":"10.3390","volume":"27","author":[{"given":"Saleem H.","family":"Aladaileh","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-6925","authenticated-orcid":false,"given":"Mohammad H.","family":"Abukhalil","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal A.","family":"Alfwuaires","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmohsen I.","family":"Algefare","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8458-7803","authenticated-orcid":false,"given":"Mohd Rasheeduddin","family":"Imran","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayeeda","family":"Anjum","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5607-5770","authenticated-orcid":false,"given":"Shatha","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5678-6896","authenticated-orcid":false,"given":"Wael A.","family":"Alsubhi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5558-1680","authenticated-orcid":false,"given":"Shaik","family":"Karimulla","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayyad Hazzaa","family":"Al-Shammari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, W., Tong, L., Jin, B., and Sun, D. 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