{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:14Z","timestamp":1791417614561,"version":"4.3.3"},"reference-count":97,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Gastric ulcer is a concerning condition that affects numerous individuals globally. Omeprazole (OMP), a well-known drug for treating stomach ulcers, has been associated with several adverse effects and limited solubility. The study aimed to create an omeprazole nanosuspension (OMP-NS) with improved solubility and bioavailability. Additionally, the study investigated the potential therapeutic effects of OMP-NS on ethanol-induced gastric injury in rats, comparing it to traditional OMP therapy to identify novel therapeutic alternatives. The characterization of the OMP-NS was assessed using DLS, TEM, XRD, FTIR, UV spectrophotometric analysis, in vitro release studies, and entrapment efficiency (EE) assays. A total of 24 male Wistar albino rats (weighing 150\u2013200 g, aged 8\u201310 weeks) were randomly divided into four groups (six rats\/group). Gastric injury was induced using absolute ethanol (5 mL\/kg), followed by oral administration of either OMP or OMP-NS (20 mg\/kg) for 7 days. Data were analyzed using one-way ANOVA accompanied by the Bonferroni post hoc test or the Kruskal\u2013Wallis test, based on data distribution, with significance set at p &lt; 0.05. The OMP-NS demonstrated a Z-average diameter of 216.1 nm, a polydispersity index of 0.2, and a zeta potential of \u221219.6 mV. The particles were predominantly spherical with an average size of 67.28 nm. In vitro release studies showed 97.78% release at 8 h, with an EE% of 96.97%. Ethanol-induced gastric ulcers were associated with oxidative stress, characterized by elevated levels of NADPH, ROS, MDA, and NO, while the level of SOD was reduced. It was accompanied by increased inflammatory markers HMGB1, which subsequently increased TLR-2, MyD88, NF-\u03baBp56, NLRP3, TNF-\u03b1, IL-1\u03b2, and IL-6 levels; conversely, a significant decrease in Nrf2\/PPAR-\u03b3\/SIRT1 levels was observed. In contrast, OMP-NS administration significantly reduced oxidative stress and inflammatory markers, restored SOD activity, and upregulated protective pathways Nrf2\/PPAR-\u03b3\/SIRT1 more effectively than conventional OMP therapy. In conclusion, OMP-NS represents a promising therapeutic strategy with notable anti-inflammatory and anti-ulcerogenic effects in ethanol-induced gastric ulcers.<\/jats:p>","DOI":"10.3390\/biom15060902","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T09:57:48Z","timestamp":1750327068000},"page":"902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Enhanced Therapeutic Efficacy of Omeprazole Nanosuspension in Ethanol-Induced Gastric Ulcer: A Focus on Oxidative Stress and Inflammatory Pathways"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4955-5705","authenticated-orcid":false,"given":"Mody","family":"Albalawi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1524-7247","authenticated-orcid":false,"given":"Sahar","family":"Khateeb","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Biochemistry Division, Department of Chemistry, Faculty of Science, Fayoum University, Fayoum 63514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s12262-021-03189-z","article-title":"The global prevalence of peptic ulcer in the world: A systematic review and meta-analysis","volume":"84","author":"Salari","year":"2022","journal-title":"Indian J. 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