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Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL\/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg\/kg), and 4% milk kefir (Kefir; 0.3 mL\/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg\/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-\u03b1 levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1\u201335 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-\u03b1 systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.<\/jats:p>","DOI":"10.3390\/cells12242799","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T08:47:26Z","timestamp":1702025246000},"page":"2799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers"],"prefix":"10.3390","volume":"12","author":[{"given":"Larissa Zambom","family":"C\u00f4co","sequence":"first","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Aires","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glaucimeire Rocha","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduarda de Souza","family":"Belis\u00e1rio","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9646-3944","authenticated-orcid":false,"given":"Michelle Khai Khun","family":"Yap","sequence":"additional","affiliation":[{"name":"School of Science, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1453-3185","authenticated-orcid":false,"given":"Fernanda Gobbi","family":"Amorim","sequence":"additional","affiliation":[{"name":"Laboratory of Mass Spectrometry, Department of Chemistry, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-479X","authenticated-orcid":false,"given":"Javier","family":"Conde-Aranda","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Gastroenterology, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breno Valentim","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Morphology, Health Sciences Center, Federal University of Esp\u00edrito Santo (UFES), Vitoria 29047-105, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7169-5634","authenticated-orcid":false,"given":"Elisardo Corral","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago de Melo Costa","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-4892","authenticated-orcid":false,"given":"Bianca Prandi","family":"Campagnaro","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bindu, S., Mazumder, S., and Bandyopadhyay, U. 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