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Epidermis: a site of drug metabolism in neonatal rat skin. Studies on cytochrome P-450 content and mixed-function oxidase and epoxide hydrolase activity.

Authors
Bickers-DR; Dutta-Choudhury-T; Mukhtar-H
Source
Mol Pharmacol 1982 Jan; 21(1):239-247
NIOSHTIC No.
00187026
Abstract
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.
Keywords
NIOSH-Publication; NIOSH-Grant; Dermatitis; Laboratory-animals; Skin-exposure; Metabolic-study; Enzyme-activity
Contact
Medicine Cleveland V a Hospital 10701 East Blvd Cleveland, Ohio 44106
CODEN
MOPMA3
Publication Date
19820101
Document Type
Journal Article
Funding Amount
267904
Funding Type
Grant
Fiscal Year
1982
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-01149
Issue of Publication
1
ISSN
0026-895X
Source Name
Molecular Pharmacology
State
OH
Performing Organization
Case Western Reserve University, Cleveland, Ohio
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