Renoprotective Effects of Vortioxetine in Experimental Renal Ischemia–Reperfusion Injury: An Investigation of Oxidative Stress, Inflammation, and Apoptotic Signaling

Renal ischemia–reperfusion (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–Dawley 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–reperfusion 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’s 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-α, IL-1β, PGC-1α, 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.