title: Reconstituted epidermis: a novel model for the study of drug metabolism in human epidermis.
abstract: The metabolic capacity of reconstituted epidermis from the outer root sheath cells of human hair follicles was determined. It was found that this epidermis possesses enzymes involved in both phase I (oxidation) and phase II (conjugation) reactions for drug biotransformation. The use of model substrates allowed the characterization of several isoenzymes. The homogenate fraction contained membrane-bound mixed-function oxydases (cytochrome P-450 dependent) involved in the O-dealkylation of 7-ethoxy-, 7-pentoxy-, and 7-benzoxyresorufin, NADPH cytochrome c (P-450) reductase, testosterone 5 alpha-reductase, and UDP-glucuronosyltransferases, which conjugate 1-naphthol and bilirubin. One isoform of each glutathione S-transferase, steroid-, and arylsulfatases, acting on estrone- and 4-methylumbelliferone sulfates, was detected. Additionally, the activity of two distinct forms of epoxide hydrolases, which hydrate cis- and trans-stilbene oxides, could be measured. The presence of these drug metabolizing enzymes in the reconstituted epidermis indicates that it has a potential to serve as a model to study epidermal drug metabolism in vitro.
authors.affiliation: Centre du Médicament Nancy, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Pham
authors.forename: J
authors.initials: J
authors.lastname: Magdalou
authors.forename: G
authors.initials: G
authors.lastname: Siest
authors.forename: M C
authors.initials: MC
authors.lastname: Lenoir
authors.forename: B A
authors.initials: BA
authors.lastname: Bernard
authors.forename: J C
authors.initials: JC
authors.lastname: Jamoulle
authors.forename: B
authors.initials: B
authors.lastname: Shroot
mesh_terms: D001192:Arylsulfatases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004817:Epidermis / Q000201:enzymology / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006197:Hair / Q000378:metabolism; D006652:Histological Techniques; D006801:Humans; D008954:Models, Biological; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D043266:Steryl-Sulfatase
chemical_list: D004852:Epoxy Compounds; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D014453:Glucuronosyltransferase; D001192:Arylsulfatases; D043266:Steryl-Sulfatase