Epidermis: a site of drug metabolism in neonatal rat skin. Studies on cytochrome P-450 content and mixed-function oxidase and epoxide hydrolase activity.
Bickers-DR; Dutta-Choudhury-T; Mukhtar-H
Mol Pharmacol 1982 Jan; 21(1):239-247
A technique developed for separating the epidermis and dermis using dithiothreitol was used to assess carefully the comparative activity of microsomal drug metabolizing enzymes, the hemoprotein cytochrome- P-450, and epoxide-hydrolase in epidermis and dermis of neonatal rat skin. Four day old Sprague-Dawley-rats pretreated with a cutaneous application of Aroclor-1254 were killed, and the skin was removed. Whole skin, epidermis and dermis were tested for enzyme activity. Quantitative carbon-monoxide-dithionite-reduced minus dithionite- reduced difference spectra were obtained only from Aroclor-1254 treated epidermal microsomes. Cytochrome-P-450 concentrations in epidermal microsomes from Aroclor treated neonatal rats were 17.8 and 40.5 picomoles/milligram of protein, respectively, when estimated using carbon-monoxide-dithionite-reduced minus dithionite- reduced and carbon-monoxide-dithionite-reduced minus carbon-monoxide- reduced difference spectra. Aryl-hydrocarbon-hydroxylase, 7- ethoxycoumarin O-deethylase, and epoxide-hydrolase activities were highest in epidermis as compared with dermis or whole skin when expressed as product per minute per milligram of protein or product per minute per gram of tissue. The results indicated that the skin has the capacity to metabolize xenobiotics and that epidermis, often considered to be metabolically inert, is an active site of such enzyme activity.
NIOSH-Publication; NIOSH-Grant; Dermatitis; Laboratory-animals; Skin-exposure; Metabolic-study; Enzyme-activity
Medicine Cleveland V a Hospital 10701 East Blvd Cleveland, Ohio 44106
Case Western Reserve University, Cleveland, Ohio