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The study aims to protect against gastric hyperacidity without interfering with gastric acid secretion. Pylorus ligation\u2013induced hyperacidity is commonly utilized in the induction of gastric ulcers.<\/jats:p>\n                  <jats:p>\n                    Forty-two rats were distributed into seven groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096). Group I comprised sham-operated group. Group II served as pylorus-ligation group. Groups III\u2013VII were given oral Linagliptin (LN; 3 and 6\u00a0mg\/kg), L-arginine (LA; 150 and 300\u00a0mg\/kg) and their combination (LN 3\u2009+\u2009LA 150\u00a0mg\/kg), respectively for 7\u00a0days. On the 8\n                    <jats:sup>th<\/jats:sup>\n                    day, groups II\u2013VII were subjected to pylorus-ligation.\n                  <\/jats:p>\n                  <jats:p>Treatment of pylorus-ligated rats with LN, LA and their combination improved the gastric hyperacidity as exhibited by a marked reduction in the gastric juice volume, total and free acidities and pepsin contents with a noticeable increase in pH. Pre-treatment with LN, LA and their combination showed a marked alleviation in the gastric inflammatory indicators evidenced by reduction in the gastric levels of MCP-1and Il-1\u03b2 as well as elevation of eNOS levels versus the sham-operated group. A marked up-regulation in the gastric gene expression of PGE, EP4 and VEGF accompanied by an improvement of the histopathologic pictures\/scores, and TNF-\u03b1 and caspase-3 immuno-staining were also recorded.<\/jats:p>\n                  <jats:p>By estimating the combination-index, it can be concluded that combining LN with LA exhibited prophylactic synergistic effects in ameliorating pylorus ligated-induced hyperacidity, mainly via up-regulation of EP4 receptor and improvement of vascular endothelial damage through VEGF expression in gastric mucosa.<\/jats:p>","DOI":"10.1007\/s00210-023-02667-3","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T06:02:13Z","timestamp":1692856933000},"page":"1127-1139","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["RETRACTED ARTICLE: Pylorus ligation-induced hyperacidity: synergistic prophylactic effects of linagliptin and L-arginine via up-regulation of EP4 receptor subtype and improvement of vascular endothelial damage"],"prefix":"10.1007","volume":"397","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-5968","authenticated-orcid":false,"given":"Gihan F.","family":"Asaad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-5422","authenticated-orcid":false,"given":"Dalia O.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-350X","authenticated-orcid":false,"given":"Rasha E.","family":"Mostafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7641-3504","authenticated-orcid":false,"given":"Azza","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2445-3314","authenticated-orcid":false,"given":"Gehad Abdel","family":"Jaleel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"2667_CR1","doi-asserted-by":"publisher","first-page":"e0216737","DOI":"10.1371\/journal.pone.0216737","volume":"14","author":"MS Abdelfattah","year":"2019","unstructured":"Abdelfattah MS, Elmallah MI, Ebrahim HY, Almeer RS, Eltanany RM, Abdel Moneim AE (2019) Prodigiosins from a marine sponge-associated actinomycete attenuate HCl\/ethanol-induced gastric lesion via antioxidant and anti-inflammatory mechanisms. 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Please see the Retraction Notice for more detail:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00210-026-05900-x","URL":"https:\/\/doi.org\/10.1007\/s00210-026-05900-x","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experiments were done following the recommendations of the National Institutes of Health Guide for Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978) and after the approval of the National Research Centre\u2013Medical Research Ethics Committee (NRC-MREC) for the use of animal subjects (Approval no. 3241052021).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors agreed with the content and that all gave explicit consent to submit and publish.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}