{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:44:59Z","timestamp":1785415499213,"version":"3.56.0"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"crossref","award":["2021\/43\/O\/NZ7\/00690"],"award-info":[{"award-number":["2021\/43\/O\/NZ7\/00690"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2021\/43\/O\/NZ7\/00690"],"award-info":[{"award-number":["2021\/43\/O\/NZ7\/00690"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Intestinal dysfunction and parenteral nutrition (PN) can trigger a spectrum of liver disorders collectively referred to as intestinal failure-associated liver disease (IFALD), for which therapeutic options remain limited. In the present study, we investigated the modulatory effects of the bioactive xanthophyll carotenoid lutein in an in vitro IFALD model utilizing human THLE-2 hepatocytes exposed to lipopolysaccharide and Intralipid to mimic PN\u2013associated inflammatory and metabolic stress. Because lutein is poorly water-soluble and patients receiving PN lack enteral intake of this compound, we also evaluated the cyto- and hemocompatibility of a human serum albumin\u2013based lutein nanoformulation developed to enable intravenous administration. A bead-based multiplex immunoassay revealed that lutein attenuated dysregulation of inflammatory and metabolic signaling by modulating total and phosphorylated levels of MAPKs, NF-\u03baB, Akt, STAT5, CREB, and p70S6K. Lutein also affected lipid metabolism\u2013related gene expression, decreasing SREBF2 and restoring ABCA1 and PRKAA2 mRNA toward control levels, as determined by qPCR. Nanoformulated lutein, with a mean particle size of approximately 160 nm, was non-toxic in THLE-2 cells and exhibited hemocompatibility in a human erythrocyte hemolysis assay. Together, our findings provide both biological and technological rationale for further exploration of lutein-based strategies to mitigate IFALD in patients receiving PN.<\/jats:p>","DOI":"10.3390\/molecules31091413","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:28:23Z","timestamp":1777040903000},"page":"1413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lutein Modulates Stress-Responsive Signaling Pathways in THLE-2 Human Hepatocytes Under Intestinal Failure\u2013Associated Liver Disease Conditions"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3422-7441","authenticated-orcid":false,"given":"Izabela","family":"\u017b\u00f3\u0142nowska","sequence":"first","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Chemistry, Rokietnicka 3, 60-806 Poznan, Poland"},{"name":"Poznan University of Medical Sciences, Doctoral School, Bukowska 70, 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7275-0298","authenticated-orcid":false,"given":"Violetta","family":"Krajka-Ku\u017aniak","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9106-8961","authenticated-orcid":false,"given":"Marta","family":"Belka","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Doctoral School, Bukowska 70, 60-812 Poznan, Poland"},{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2654-1764","authenticated-orcid":false,"given":"Grzegorz","family":"Adamek","sequence":"additional","affiliation":[{"name":"Faculty of Materials Engineering and Technical Physics, Institute of Materials Science and Engineering, Poznan University of Technology, Jana Paw\u0142a II No. 24, 61-139 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-5937","authenticated-orcid":false,"given":"Maciej","family":"Stawny","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Chemistry, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/ncp.11116","article-title":"Intestinal Failure\u2013Associated Liver Disease: Current Challenges in Screening, Diagnosis, and Parenteral Nutrition Considerations","volume":"39","author":"Tabone","year":"2024","journal-title":"Nutr. 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