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

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.

Fucoxanthin for Topical Administration, a Phototoxic vs. Photoprotective Potential in a Tiered Strategy Assessed by In Vitro Methods

“…Thus, although Rodríguez-Luna et al [48] obtained valuable information from hairless mice, it is well known that human adverse events cannot always be detected in animals, due to inherent genetic and physiological differences between species and that skin model constructed with human cells and physiologic relevant microarchitecture contributes to the better prediction of human effects. In the previous study of our group, commercial fucoxanthin at the same concentration, presented an absence of irritation, absence of morphological changes in the histology, and no significant dysregulation on homeostasis, metabolism, and in the inflammatory genes studied after following the OECD protocol for skin irritation [49].…”

Advances in Studies on the Pharmacological Activities of Fucoxanthin

“…Its molecular weight is very small and can be easily absorbed by the organism. Fucoxanthin is not toxic to human skin cells, liver, kidney, spleen, and gonadal tissue, and, therefore, can have several applications [ 2 , 3 ]. However, due to the presence of a large number of unsaturated bonds, fucoxanthin is rather unstable.…”

Fucoxanthin Ameliorates Atopic Dermatitis Symptoms by Regulating Keratinocytes and Regulatory Innate Lymphoid Cells

“…We propose here that FX would help to improve AD symptoms more effectively by regulating ILCreg in the skin. The safety of FX was confirmed in a three-dimensional skin model [50]. Although our results may not currently be extrapolatable to humans, they still show that FX has the potential to become a new option for AD prevention and treatment.…”