Korean J Physiol Pharmacol.  2001 Oct;5(5):407-412.

Constitutive expression and changes of cytochrome P450 isozymes mRNAs by vehicles (petrolatum, DMSO, ethanol) in rat skin using semi-quantitative RT-PCR

• Lee AY
• Lee KH
• Ko DS
• Chey WY

Abstract

Many drugs are primarily metabolized by the cytochrome P450s (CYPs). Drug metabolites would be important allergens for adverse drug reactions such as drug eruptions. Skin tests with a suspected drug have conducted to identify causative drugs of drug eruptions, with vehicles such as white petrolatum, DMSO, ethanol. This study will compare the expression of rat CYP isozyme mRNAs between the skin and the liver, with examining an effect of the vehicles on the cutaneous CYPs using semi-quantitative RT-PCR. Thirty-two Sprague-Dawley rats between the ages of six and eight weeks were divided as four groups. One group was used to compare the constitutive mRNA expression between skin and liver, while the others were to examine the effects of three vehicles. The ratios of expression of CYP1A2, CYP2B1/2, CYP2E1, CYP3A1, and CYP4A1 were significantly higher in the liver than the skin. However, CYP1A1 and CYP2C11 were higher in the skin than liver. The effects of vehicles were quite different; white petrolatum significantly induced CYP1A1 (p=0.012) and CYP2C11 mRNAs, while ethanol inhibited CYP1A1 and CYP2B1/2. DMSO did not make any changes. The results suggest that rat skin can participate in drug metabolism with their own CYP isozymes. The effects of vehicles on the cutaneous CYP expression should not be ignored and may be applied for determination of an appropriate vehicle for certain drug(s).

MeSH Terms

Allergens
Animals
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP2E1
Cytochrome P-450 Enzyme System*
Cytochromes*
Dimethyl Sulfoxide*
Drug Eruptions
Drug-Related Side Effects and Adverse Reactions
Ethanol
Isoenzymes*
Liver
Metabolism
Petrolatum
Rats*
Rats, Sprague-Dawley
RNA, Messenger*
Skin Tests
Skin*
Allergens
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP2E1
Cytochrome P-450 Enzyme System
Cytochromes
Dimethyl Sulfoxide
Ethanol
Isoenzymes
Petrolatum
RNA, Messenger