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Article

Skin Irritation Testing beyond Tissue Viability: Fucoxanthin Effects on Inflammation, Homeostasis, and Metabolism

1
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Monte Alegre, Ribeirão Preto, SP 14040-903, Brazil
2
Clinical and Toxicological Analyses Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, São Paulo, SP 05508-000, Brazil
3
Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, São Paulo, SP 05508-000, Brazil
4
Institute of Pharmacy (Pharmacology & Toxicology), Freie Universität Berlin, Königin Luise Str 2+4, 14195 Berlin, Germany
5
TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(2), 136; https://doi.org/10.3390/pharmaceutics12020136
Received: 20 November 2019 / Revised: 27 January 2020 / Accepted: 31 January 2020 / Published: 5 February 2020
(This article belongs to the Special Issue Drug Delivery across Biological Barriers)
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-1α, 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. View Full-Text
Keywords: antioxidants; epidermal growth factor receptor; interleukins; irritation; metabolism response; N-acetyltransferase; small heat and shock protein beta 1 antioxidants; epidermal growth factor receptor; interleukins; irritation; metabolism response; N-acetyltransferase; small heat and shock protein beta 1
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MDPI and ACS Style

Spagolla Napoleão Tavares, R.; Stuchi Maria-Engler, S.; Colepicolo, P.; Debonsi, H.M.; Schäfer-Korting, M.; Marx, U.; Rigo Gaspar, L.; Zoschke, C. Skin Irritation Testing beyond Tissue Viability: Fucoxanthin Effects on Inflammation, Homeostasis, and Metabolism. Pharmaceutics 2020, 12, 136. https://doi.org/10.3390/pharmaceutics12020136

AMA Style

Spagolla Napoleão Tavares R, Stuchi Maria-Engler S, Colepicolo P, Debonsi HM, Schäfer-Korting M, Marx U, Rigo Gaspar L, Zoschke C. Skin Irritation Testing beyond Tissue Viability: Fucoxanthin Effects on Inflammation, Homeostasis, and Metabolism. Pharmaceutics. 2020; 12(2):136. https://doi.org/10.3390/pharmaceutics12020136

Chicago/Turabian Style

Spagolla Napoleão Tavares, Renata, Silvya Stuchi Maria-Engler, Pio Colepicolo, Hosana M. Debonsi, Monika Schäfer-Korting, Uwe Marx, Lorena Rigo Gaspar, and Christian Zoschke. 2020. "Skin Irritation Testing beyond Tissue Viability: Fucoxanthin Effects on Inflammation, Homeostasis, and Metabolism" Pharmaceutics 12, no. 2: 136. https://doi.org/10.3390/pharmaceutics12020136

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