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

Author(s)

Spagolla Napoleao Tavares, Renata ^[1] ; Stuchi Maria-Engler, Silvya ^[2] ; Colepicolo, Pio ^[3] ; Debonsi, Hosana Maria ^[1] ; Schaefer-Korting, Monika ^[4] ; Marx, Uwe ^[5] ; Rigo Gaspar, Lorena ^[1] ; Zoschke, Christian ^[4]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Clin & Toxicol Anal Dept, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Chem, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

^[4] Free Univ Berlin, Inst Pharm Pharmacol & Toxicol, Konigin Luise Str 2 4, D-14195 Berlin - Germany

^[5] TissUse GmbH, Oudenarder Str 16, D-13347 Berlin - Germany

• Document type: Journal article
• Source: PHARMACEUTICS; v. 12, n. 2 FEB 2020.
• Web of Science Citations: 0

Abstract

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 alpha, 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. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/06931-4 - Biodiversity of marine algae and metabolites of economical impact
• Grantee: Pio Colepicolo Neto
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants