Drug metabolism in skin. Comparative activity of the mixed-function oxidases, epoxide hydratase, and glutathione S-transferase in liver and skin of the neonatal rat.
Mukhtar H; Bickers DR
Drug Metab Dispos 1981 Jul; 9(4):311-314
The activity of aryl-hydrocarbon-hydroxylase (AH) in skin was compared with its activity in other organs following topical application of cutaneous enzyme system inducers. Newborn rats were treated with 100 milligrams per kilogram (mg/kg) skin application of polychlorinated biphenyls (PCB), Aroclor-1254 (11097691), or benz(a)pyrene (50328) (BaP). After 24 hours, animals were killed and skin, liver, lungs, kidneys, intestines, and remaining carcass were prepared for enzyme assay. After topical application of BaP, there was induction of AH in each tissue studied. A greater increase in enzyme activity in skin as compared with other extrahepatic tissues was observed. When total organ activities were compared with respect to the whole body, whole body activity was greater than in liver, which was greater than in skin. After topical application of Aroclor, there were increases in AH activities and 7-ethoxycoumarin deethylase in skin and liver. Glutathione-S-transferase (GSH) activity in neonatal rat liver was induced 40 to 60 percent over controls after application of Aroclor. Cutaneous GSH activity did not increase after skin application of Aroclor. The authors conclude that the topical application of PCB to neonatal rats results in the doubling of hepatic/extrahepatic activities without any detectable effect on the skin enzymes.
NIOSH-Publication; NIOSH-Grant; Enzyme-activity; Animal-studies; Skin-exposure; Medical-research; Analytical-methods; Metabolic-study; Biological-effects; Physiological-response; Laboratory-techniques
Medicine Cleveland V a Hospital 10701 East Blvd Cleveland, Ohio 44106
Drug Metabolism and Disposition
Case Western Reserve University, Cleveland, Ohio