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Male Sprague-Dawley rats were randomly assigned to control, saline-treated ulcer, xenin-25-treated ulcer groups. Gastric ulcer was induced with indomethacin (25\u00a0mg\/kg, subcutaneously) and xenin-25 (0.2, 2, 20\u00a0\u00b5g\/kg) or saline was given subcutaneously immediately after and at 2\u00a0h following indomethacin injection. In order to investigate whether the effects of xenin-25 depend on vagal afferent fibres, two additional groups underwent vagal afferent denervation (VAD) by bilateral perivagal capsaicin application (1%). Following a 2-week recovery, rats with VAD were induced with ulcer, after which they received either xenin-25 (2\u00a0\u00b5g\/kg) or saline. All animals were sacrificed 4\u00a0h after ulcer induction, and gastric tissues were collected for biochemical, molecular, and histopathological analyses. Indomethacin administration resulted in significant increases in malondialdehyde and myeloperoxidase levels, accompanied by glutathione depletion, upregulation of\n                    <jats:italic>nuclear factor-\u03baB<\/jats:italic>\n                    and\n                    <jats:italic>Bax<\/jats:italic>\n                    , and downregulation of\n                    <jats:italic>Bcl2<\/jats:italic>\n                    expression. Xenin-25 treatment markedly attenuated oxidative stress, inflammatory responses, apoptotic markers, and histopathological gastric damage. Xenin-25-induced reductions in lesion length, malondialdehyde, and myeloperoxidase levels were abolished in VAD rats, but all the other anti-inflammatory and anti-apoptotic effects of Xenin-25 were preserved even in the absence of vagal afferents. Xenin-25 exhibits gastroprotective effects in acute gastric injury through its antioxidant, anti-inflammatory, and anti-apoptotic actions, which are independent of vagal afferent fibers.\n                  <\/jats:p>","DOI":"10.1007\/s00424-026-03186-9","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:11:29Z","timestamp":1780967489000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Xenin-25 improves indomethacin-induced acute gastric injury in rats"],"prefix":"10.1007","volume":"478","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-1450","authenticated-orcid":false,"given":"Sevil","family":"Arabac\u0131 Tamer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"G\u00fcney Eskiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feriha","family":"Ercan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berrak","family":"\u00c7. 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