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    Naringenin protects against renal ischemia–reperfusion injury following unilateral nephrectomy via modulation of oxidative stress and kisspeptin expression
    (Springer Nature, 16.07.2026) Sahin‑Buyukkorkmaz, Leyla; Taşdemir, Seda; Özhan, Onural; Eranıl, Işıl; Tanbek, Kevser; Vardi, Nigar; Gozukara‑Bag, Harika Gozde; Acet, Ahmet; Parlakpınar, Hakan
    Abstract Background Renal ischemia–reperfusion (IR) injury is a major cause of acute kidney injury, mediated by oxidative stress (OS), inflammation, and apoptosis. Naringenin (NRG), a citrus flavonoid, exerts antioxidant and anti-apoptotic actions, yet its role in renal kisspeptin signaling during IR injury remains unexplored. This study investigated the protective effects of NRG on renal IR injury in rats, with emphasis on OS, apoptosis, and kisspeptin expression. Methods Thirty-two female Wistar albino rats were randomized into four groups: sham, IR, NRG/IR (100 mg/kg NRG administered 2 h before ischemia), and IR/NRG (NRG given at reperfusion). Following right nephrectomy and 60 min ischemia of the left kidney, reperfusion was allowed for 24 h. Serum (blood urea nitrogen, creatinine, albumin), tissue OS markers, histopathology, and immunohistochemical expression of kisspeptin, Bcl-2-associated X (Bax), and B cell lymphoma 2 (Bcl-2) were evaluated. Results IR markedly increased malondialdehyde and reduced superoxide dismutase and catalase activities, accompanied by tubular degeneration, congestion, and dilatation. NRG treatment significantly reversed these biochemical and histological changes. Pre-ischemic NRG enhanced Bcl-2 immunoreactivity, while post-ischemic administration restored kisspeptin expression. Bax expression showed only mild non-significant increases. Notably, post-treatment provided superior recovery of kisspeptin signaling and structural preservation, whereas pre-treatment more effectively enhanced anti-apoptotic protein expression. Conclusion NRG confers renoprotection against IR injury by reducing OS, preserving renal architecture, and modulating apoptosis-related proteins. A novel finding is the restoration of kisspeptin expression by NRG, particularly when administered at reperfusion, suggesting timing-dependent therapeutic potential. Keywords Renal ischemia–reperfusion · Naringenin · Oxidative stress · Apoptosis · Kisspeptin