{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:44:46Z","timestamp":1788425086218,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationEU","award":["PE00000003"],"award-info":[{"award-number":["PE00000003"]}]},{"name":"European Union\u2014NextGenerationEU","award":["D93C22000890001"],"award-info":[{"award-number":["D93C22000890001"]}]},{"name":"Italian Ministry of University and Research","award":["PE00000003"],"award-info":[{"award-number":["PE00000003"]}]},{"name":"Italian Ministry of University and Research","award":["D93C22000890001"],"award-info":[{"award-number":["D93C22000890001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Phenylalanine (Phe)-free protein substitutes (PSs) are used to provide an adequate intake of amino acids (AAs), except Phe, allowing control of blood Phe levels in patients with Phenylketonuria (PKU). Although indicated as a standard dietary treatment for these patients, free AAs mixtures are not absorbed as natural proteins, thus creating an oxidized and inflamed state in the intestine. Nowadays, PSs on the market also include slow-release amino acids (SR-AAs) formulas. The present work aims to investigate the effects of an SR-AAs formula on both oxidative and inflammatory status in human intestinal Caco-2 cells, comparing its mechanism of action with that of a mixture of free AAs. In more detail, oxidative stress and inflammation were induced at the cellular level using H2O2 and lipopolysaccharides (LPSs), respectively, and both free AAs and SR-AAs PSs were tested to evaluate if they were able to restore a more balanced condition. According to our findings, free AAs aggravate the intestinal oxidative and inflammatory status caused by H2O2 and LPS in human intestinal Caco-2 cells, which SR-AAs significantly improve. In conclusion, our results offer preclinical novelty on these products\u2019 mechanisms of action, thus improving the dietary management of patients with PKU.<\/jats:p>","DOI":"10.3390\/antiox14030271","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T04:46:37Z","timestamp":1740545197000},"page":"271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Antioxidant and Anti-Inflammatory Activity of a New Formulation of Slow-Release Amino Acids in Human Intestinal Caco-2 Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5698-1325","authenticated-orcid":false,"given":"Carlotta","family":"Bollati","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-5288","authenticated-orcid":false,"given":"Martina","family":"Tosi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vittore Buzzi Children\u2019s Hospital, University of Milan, 20154 Milan, Italy"},{"name":"Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3356-0595","authenticated-orcid":false,"given":"Lorenza","family":"d\u2019Adduzio","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3175-924X","authenticated-orcid":false,"given":"Melissa","family":"Fanzaga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-137X","authenticated-orcid":false,"given":"Alberto","family":"Burlina","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Women\u2019s and Children\u2019s Health, Reference Centre Expanded Newborn Screening, University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2795-9874","authenticated-orcid":false,"given":"Gianvincenzo","family":"Zuccotti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vittore Buzzi Children\u2019s Hospital, University of Milan, 20154 Milan, Italy"},{"name":"Department of Biomedical and Clinical Science, University of Milan, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-4486","authenticated-orcid":false,"given":"Carmen","family":"Lammi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2111-3111","authenticated-orcid":false,"given":"Elvira","family":"Verduci","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milan, 20142 Milan, Italy"},{"name":"Metabolic Diseases Unit, Department of Pediatrics, Vittore Buzzi Children\u2019s Hospital, University of Milan, 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-017-0685-2","article-title":"The Complete European Guidelines on Phenylketonuria: Diagnosis and Treatment","volume":"12","author":"MacDonald","year":"2017","journal-title":"Orphanet J. 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