{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:30Z","timestamp":1787029350651,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/06931-4"],"award-info":[{"award-number":["2016\/06931-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031A262A"],"award-info":[{"award-number":["031A262A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["465687\/2014-8"],"award-info":[{"award-number":["465687\/2014-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["290281\/2017-2"],"award-info":[{"award-number":["290281\/2017-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>UV light catalyzes the ozone formation from air pollutants, like nitrogen oxides. Since ozone reacts with cutaneous sebum lipids to peroxides and, thus, promotes inflammation, tumorigenesis, and aging, even broad-spectrum sunscreens cannot properly protect skin. Meanwhile, xanthophylls, like fucoxanthin, proved their antioxidant and cytoprotective functions, but the safety of their topical application in human cell-based models remains unknown. Aiming for a more detailed insight into the cutaneous fucoxanthin toxicity, we assessed the tissue viability according to OECD test guideline no. 439 as well as changes in inflammation (IL-1\u03b1, IL-6, IL-8), homeostasis (EGFR, HSPB1) and metabolism (NAT1). First, we proved the suitability of our 24-well-based reconstructed human skin for irritation testing. Next, we dissolved 0.5% fucoxanthin either in alkyl benzoate or in ethanol and applied both solutions onto the tissue surface. None of the solutions decreased RHS viability below 50%. In contrast, fucoxanthin ameliorated the detrimental effects of ethanol and reduced the gene expression of pro-inflammatory interleukins 6 and 8, while increasing NAT1 gene expression. In conclusion, we developed an organ-on-a-chip compatible RHS, being suitable for skin irritation testing beyond tissue viability assessment. Fucoxanthin proved to be non-irritant in RHS and already showed first skin protective effects following topical application.<\/jats:p>","DOI":"10.3390\/pharmaceutics12020136","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T02:59:18Z","timestamp":1580957958000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Skin Irritation Testing beyond Tissue Viability: Fucoxanthin Effects on Inflammation, Homeostasis, and Metabolism"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8491-2319","authenticated-orcid":false,"given":"Renata","family":"Spagolla Napole\u00e3o Tavares","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Av. do Caf\u00e9 s\/n, Monte Alegre, Ribeir\u00e3o Preto, SP 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4771-6041","authenticated-orcid":false,"given":"Silvya","family":"Stuchi Maria-Engler","sequence":"additional","affiliation":[{"name":"Clinical and Toxicological Analyses Department, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universit\u00e1ria, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pio","family":"Colepicolo","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of S\u00e3o Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universit\u00e1ria, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4888-0217","authenticated-orcid":false,"given":"Hosana Maria","family":"Debonsi","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Av. do Caf\u00e9 s\/n, Monte Alegre, Ribeir\u00e3o Preto, SP 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Sch\u00e4fer-Korting","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Pharmacology &amp; Toxicology), Freie Universit\u00e4t Berlin, K\u00f6nigin Luise Str 2+4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Marx","sequence":"additional","affiliation":[{"name":"TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Rigo Gaspar","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Av. do Caf\u00e9 s\/n, Monte Alegre, Ribeir\u00e3o Preto, SP 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2535-3606","authenticated-orcid":false,"given":"Christian","family":"Zoschke","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Pharmacology &amp; Toxicology), Freie Universit\u00e4t Berlin, K\u00f6nigin Luise Str 2+4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2147\/CCID.S44686","article-title":"Effect of the sun on visible clinical signs of aging in caucasian skin","volume":"6","author":"Flament","year":"2013","journal-title":"Clin. 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