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

Renata Spagolla Napoleão Tavares,Silvya Stuchi Maria-Engler,Monika Schäfer-Korting,Hosana Maria Debonsi,Uwe Marx,Christian Zoschke,Pio Colepicolo,Lorena Rigo Gaspar

doi:10.3390/pharmaceutics12020136

Renata Spagolla Napoleão Tavares, Silvya Stuchi Maria-Engler + Show 6 more

Open Access

https://doi.org/10.3390/pharmaceutics12020136

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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-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.

Highlights

Epidemiological data and clinical presentation provide conclusive evidence for UV radiation as the major cause of skin aging, cancer, and inflammation [1,2]
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)
Fucoxanthin ameliorated the detrimental effects of ethanol and reduced the gene expression of pro-inflammatory interleukins 6 and 8, while increasing N-acetyltransferase 1 (NAT1) gene expression

Summary

Introduction

Epidemiological data and clinical presentation provide conclusive evidence for UV radiation as the major cause of skin aging, cancer, and inflammation [1,2]. UVB radiation promote the dimerization of pyrimidine DNA bases to cyclobutane dimers and subsequently C to T base transitions. Abundant C to T base transitions and CC to TT tandem mutations are referred to as a UVB signature or fingerprint. UVA radiation increases numbers of reactive oxygen species, which oxidize DNA bases to 8-hydroxyguanine, and cause G-to-T base transversion [3]. Thereby, the production of reactive oxygen species has two major causes. UV radiation directly oxidizes the major sebum component squalene and, drives the expression of pro-inflammatory cytokines [4]. UVA reacts with nitrogen oxides and volatile organic compounds, both abundant air pollutants in urban areas, to ozone [5]. Ozone itself does not penetrate the skin, but the ozone-mediated peroxidation of unsaturated lipids on the skin’s surface induces oxidative stress and inflammatory responses in deeper skin layers [6]

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