title: Xenobiotic metabolizing enzymes in human skin and SkinEthic reconstructed human skin models.
abstract: 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.
authors: L'Oréal Research & Innovation, Aulnay-Sous-Bois, France.
authors: Joan
authors: J
authors: Eilstein
authors: L'Oréal Research & Innovation, Aulnay-Sous-Bois, France.
authors: Guillaume
authors: G
authors: Léreaux
authors: L'Oréal Research & Innovation, Aulnay-Sous-Bois, France.
authors: Eric
authors: E
authors: Arbey
authors: L'Oréal Research & Innovation, Aulnay-Sous-Bois, France.
authors: Edwige
authors: E
authors: Daronnat
authors: Newcastle University, Newcastle upon, Tyne, UK.
authors: Simon
authors: S
authors: Wilkinson
authors: L'Oréal Research & Innovation, Aulnay-Sous-Bois, France.
authors: Daniel
authors: D
authors: Duché
mesh_terms: D003358:Cosmetics / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism*; D023822:Tissue Engineering; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D003358:Cosmetics; D015262:Xenobiotics
keywords: extrahepatic organ; reconstructed human skin models; skin metabolism