{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:06:38Z","timestamp":1787238398900,"version":"build-2736575974"},"reference-count":46,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Cir. Bras."],"abstract":"<jats:p>ABSTRACT  Purpose: To investigate the potential pleiotropic effects of liraglutide (LG), a glucagon-like-peptide-1 analog, on gastric ulcer prevention in rats with diabetes induced by streptozotocin (STZ).  Methods: We randomly divided 63 male Wistar rats into seven groups. STZ was administered intraperitoneally (IP) to the animals in the diabetic control (group STZ), diabetic control + indomethacin (INDO) (group STZI), STZ + INDO + omeprazole (group OMP), STZ + INDO + LG (0.2 mg\/kg) (group 0.2LG), and STZ + INDO + LG (0.4 mg\/kg) group (group 0.4LG). We administered OMP IP to group OMP, 0.2 mg\/kg LG to group 0.2LG SC, 0.4 mg\/kg LG to group 0.4LG SC, normal saline to non-diabetic control (sham group), group STZ, non-diabetic control + INDO (group KI), and group STZI SC. INDO was administered to the animals in groups KI, STZI, OMP, 0.2LG, and 0.4LG by gavage. Then, the caspase-3, epidermal growth factor (EGF), vascular endothelial growth factor-A (VEGF-A), prostaglandin E2 (PGE2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u03b1), superoxide dismutase-1 (SOD-1), glutathione (GSH), and malondialdehyde (MDA) levels were studied.  Results: LG prevented INDO-induced ulcers and decreased apoptosis in the stomach tissue. It increased the SOD-1, GSH, EGF, VEGF-A, and PGE2 levels, and reduced the MDA, IL-6, and TNF-\u03b1 levels. The anti-ulcer effect of LG was lower, but close to that of OMP.  Conclusion: The antioxidant, anti-inflammatory, and anti-apoptotic effects of LG, its ability to regulate EGF, VEGF-A, and PGE2 levels, and its capacity to reduce blood glucose levels in diabetic rats may contribute to its anti-ulcer effect.<\/jats:p>","DOI":"10.1590\/acb407325","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T15:03:36Z","timestamp":1759158216000},"source":"Crossref","is-referenced-by-count":3,"title":["The effect of liraglutide, a GLP-1 analog, on indomethacin-induced gastric ulcers in diabetic rats"],"prefix":"10.1590","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3937-825X","authenticated-orcid":false,"given":"Huseyin Emre","family":"Arslan","sequence":"first","affiliation":[{"name":"K\u00fctahya Health Sciences University,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-3621","authenticated-orcid":false,"given":"Yasemin","family":"Teksen","sequence":"additional","affiliation":[{"name":"K\u00fctahya Health Sciences University,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4662-6493","authenticated-orcid":false,"given":"Orhan","family":"Ozatik","sequence":"additional","affiliation":[{"name":"K\u00fctahya Health Sciences University,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2152-878X","authenticated-orcid":false,"given":"Mustafa Cem","family":"Algin","sequence":"additional","affiliation":[{"name":"Eskisehir City Hospital,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4183\/aeb.2018.453","article-title":"The effect of melatonin against gastric oxidative stress and dyslipidemia in streptozotocin-induced diabetic rats","volume":"14","author":"Hadjzadeh MAR","year":"2018","journal-title":"Acta Endocrinol (Buchar)"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.jss.2014.10.019","article-title":"Curcumin-induced angiogenesis hastens wound healing in diabetic rats","volume":"193","author":"Kant V","year":"2015","journal-title":"J Surg Res"},{"issue":"11","key":"ref3","article-title":"Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats","volume":"12","author":"Chen YC","year":"2017","journal-title":"PLoS 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pathway","volume":"36","author":"Allam MM","year":"2017","journal-title":"Gen Physiol Biophys"},{"issue":"5","key":"ref41","article-title":"The beneficial effects of Agaricus blazei Murrill on hepatic antioxidant enzymes and the pancreatic tissue recovery in streptozotocin-induced diabetic rats","volume":"44","author":"Wei Q","year":"2020","journal-title":"J Food Biochem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"111904","DOI":"10.1016\/j.jep.2019.111904","article-title":"Anti-diabetic and renoprotective effects of Cassiae Semen extract in the streptozotocin-induced diabetic rats","volume":"239","author":"Wang Q","year":"2019","journal-title":"J Ethnopharmacol"},{"issue":"5","key":"ref43","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1590\/2359-3997000000188","article-title":"The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats","volume":"60","author":"Fernandes SM","year":"2016","journal-title":"Arch Endocrinol 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