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Alcohol induces gastric injury through oxidative stress, inflammation, and apoptosis, while phenytoin may have potential preventive effects in ulcer. This study aimed to evaluate the gastroprotective effects of phenytoin against ethanol-induced gastric ulcers in rats, focusing on oxidative stress, inflammatory, and apoptotic biomarkers, and to elucidate the underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-two male Wistar rats were randomly divided into four groups: control, ethanol-induced gastric ulcer (ETH), phenytoin-treated (ETH\u2009+\u2009Phen), and omeprazole-treated (ETH\u2009+\u2009Ome). Gastric ulcers were induced by oral administration of absolute ethanol. Ulcer area, gastric content volume, oxidative stress markers (TAC, MDA, GSH, SOD, CAT), inflammatory mediators (NF-\u03baB, TNF-\u03b1, IL-1\u03b2, iNOS, COX-2), and apoptotic markers (Bax, Bcl-2, Caspase-3) were measured using biochemical assays, real time PCR, and ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ethanol administration significantly increased ulcer area, gastric content volume, MDA levels, NF-\u03baB activation, pro-inflammatory cytokines, and pro-apoptotic markers, while reducing TAC, GSH, and antioxidant enzyme activities. Preventive phenytoin treatment significantly attenuated these effects, reducing ulcer area, restoring antioxidant balance, suppressing NF-\u03baB-mediated inflammation, and modulating apoptotic signaling. Both phenytoin and omeprazole improved these parameters compared with the ethanol group; however, no direct statistical comparison between the two treatments was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Phenytoin exhibits significant gastroprotective effects against ethanol-induced gastric injury, which may be associated with modulation of oxidative stress, inflammatory pathways, and apoptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40780-026-00582-2","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:23:26Z","timestamp":1780496606000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of phenytoin on ethanol-induced gastric ulceration in rats: involvement of oxidative stress, inflammation, and apoptosis"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-3993","authenticated-orcid":false,"given":"Kaveh","family":"Rahimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Najafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Fayazfard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Esmaeili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"582_CR1","doi-asserted-by":"publisher","first-page":"979","DOI":"10.3390\/molecules14030979","volume":"20","author":"K Mota","year":"2009","unstructured":"Mota K, Dias G, Pinto M, Ferreira A, Brito A, Lima Filho C: J., Batista L. 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