Reconstituted epidermis: a novel model for the study of drug metabolism in human epidermis.
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.
Pham
M A
MA
Centre du Médicament Nancy, France.
Magdalou
J
J
Siest
G
G
Lenoir
M C
MC
Bernard
B A
BA
Jamoulle
J C
JC
Shroot
B
B
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
D004852:Epoxy Compounds; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D014453:Glucuronosyltransferase; D001192:Arylsulfatases; D043266:Steryl-Sulfatase