Induction of drug metabolising enzymes in the skin by topical steroids.
The effects of the topical application of glucocorticoid steroid creams used in clinical practice, on the activity of drug metabolising enzymes in the skin of adult hairless mice has been investigated. Treatment with hydrocortisone and fluandrenolone had no effect on the activity of ethoxycoumarin O'dealkylase (EOD) in the skin whereas all other fluorinated synthetic glucocorticoids tested, significantly induced cutaneous EOD activity. Fluincinolone acetonide, Fluincinonide , and Betamethasone Valertate increased enzyme activity 2-3-fold, and clobetasol propionate induced enzyme activity 6-fold. The ability of each steroid preparation to induce enzyme activity was related to its clinical potency, and induction of enzyme activity by clobetasol propionate was maximal at 0.05%, the concentration used in clinical practice. The effects of clobetasol propionate on cutaneous ethoxycoumarin and ethoxyresorufin dealkylase activities were different from those produced by 3 methycholanthrene , indicating that glucocorticoids may represent a class of inducing agents with different properties from the polycyclic hydrocarbons.
D015660:7-Alkoxycoumarin O-Dealkylase; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002990:Clobetasol / Q000031:analogs & derivatives / Q000494:pharmacology; D003374:Coumarins / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1; D004790:Enzyme Induction; D005260:Female; D005938:Glucocorticoids; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010078:Oxazines / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis*; D010105:Oxygenases / Q000096:biosynthesis*; D012867:Skin / Q000201:enzymology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D003374:Coumarins; D005938:Glucocorticoids; D010078:Oxazines; C017299:7-ethoxycoumarin; C007649:ethoxyresorufin; D002990:Clobetasol; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1