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Xenobiotic metabolizing enzymes in human skin and SkinEthic reconstructed human skin models

Lookup NU author(s): Dr Simon Wilkinson


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© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Skin metabolism is becoming a major consideration in the development of new cosmetic ingredients, skin being the first organ exposed to them. In order to replace limited samples of Excised human skin (EHS), in vitro engineered human skins have been developed. 3D models are daily used to develop and evaluate new cosmetic ingredients and have to be characterized and compared with EHS in terms of metabolic capabilities. This work presents the determination of apparent catalytic parameters (apparent Vmax, Km and the ratio Vmax/Km) in 3D models compared with EHS for cytochrome P450 dependent monooxygenase isoforms involved in drug metabolism, esterases, alcohol dehydrogenases, aldehyde dehydrogenases, peroxidases, glutathione S-transferases, N-acetyl transferases, uridinyl diphosphate glucuronyl transferases and sulfotransferases. Results show that all these enzymes involved in the metabolism of xenobiotics are expressed and functional in the EHS and 3D models. Also, the Vmax/Km ratios (estimating the intrinsic metabolic clearances) show that the metabolic abilities are the most often comparable between the skin models and EHS. These results indicate that the 3D models can substitute themselves for EHS to select cosmetic ingredients on the basis of their metabolism, efficacy or/and safety.

Publication metadata

Author(s): Eilstein J, Lereaux G, Arbey E, Daronnat E, Wilkinson S, Duche D

Publication type: Letter

Publication status: Published

Journal: Experimental Dermatology

Year: 2015

Volume: 24

Issue: 7

Pages: 547-549

Print publication date: 01/07/2015

Online publication date: 23/03/2015

Acceptance date: 14/03/2015

ISSN (print): 0906-6705

ISSN (electronic): 1600-0625

Publisher: Blackwell Publishing Ltd


DOI: 10.1111/exd.12694

PubMed id: 25808006