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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Renal ischemia\u2013reperfusion (I\/R) injury is a leading cause of acute kidney injury and is driven by oxidative stress, sterile inflammation, and regulated cell death. Vortioxetine (VOR), a multimodal antidepressant, carries anti-inflammatory and antioxidant activity beyond its neuropsychiatric actions, but has not been tested in renal I\/R injury. Thirty-six female Sprague\u2013Dawley rats were allocated to Sham, I\/R, or VOR+I\/R (10 mg\/kg\/day by oral gavage) groups. All animals underwent right nephrectomy; in the I\/R groups the left renal artery was then clamped for 60 min and reperfused for 23 h. Renal function markers, cytokines, oxidative stress parameters, histopathology, caspase-3 immunoreactivity, and V-cam, Bax, Bcl-2, and p62\/SQSTM1 expression were assessed. Ischemia\u2013reperfusion raised serum blood urea nitrogen (BUN), V-cam and Bax expression, and caspase-3 immunoreactivity, and lowered Bcl-2 and p62\/SQSTM1; renal interleukin-6 (IL-6), unexpectedly, was lower than in Sham. VOR reduced renal malondialdehyde (MDA) and caspase-3 immunoreactivity, lowered V-cam and Bax and restored Bcl-2 and p62\/SQSTM1 in semi-quantitative immunoblots of pooled samples, and limited tubular epithelial desquamation, with Bowman\u2019s space comparable to Sham. BUN and IL-6 in VOR-treated animals were intermediate and did not differ significantly from either Sham or I\/R. Serum creatinine, TNF-\u03b1, IL-1\u03b2, PGC-1\u03b1, and most antioxidant parameters were unaffected. VOR thus produced partial, pathway-selective renoprotection rather than uniform suppression of I\/R injury. Mortality was numerically higher under VOR, so tolerability at this dose warrants dedicated evaluation.<\/jats:p>","DOI":"10.3390\/ijms27198679","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"8679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Renoprotective Effects of Vortioxetine in Experimental Renal Ischemia\u2013Reperfusion Injury: An Investigation of Oxidative Stress, Inflammation, and Apoptotic Signaling"],"prefix":"10.3390","volume":"27","author":[{"given":"Resul","family":"\u00c7i\u00e7ek","sequence":"first","affiliation":[{"name":"Department of Urology, Faculty of Medicine, \u0130n\u00f6n\u00fc University, 44280 Malatya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-0255","authenticated-orcid":false,"given":"\u0130brahim","family":"Top\u00e7u","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, \u0130n\u00f6n\u00fc University, 44280 Malatya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Bulut","family":"Dural","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, \u0130n\u00f6n\u00fc University, 44280 Malatya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2099-2273","authenticated-orcid":false,"given":"Kevser","family":"Tanbek","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, \u0130n\u00f6n\u00fc University, 44280 Malatya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Evrim","family":"Yal\u00e7\u0131n","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, \u0130n\u00f6n\u00fc University, 44280 Malatya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Nigar","family":"Vard\u0131","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, \u0130n\u00f6n\u00fc University, 44280 Malatya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-7849","authenticated-orcid":false,"given":"Onural","family":"Ozhan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, \u0130n\u00f6n\u00fc University, 44280 Malatya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1172\/JCI45161","article-title":"Cellular pathophysiology of ischemic acute kidney injury","volume":"121","author":"Bonventre","year":"2011","journal-title":"J. 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