Matt:/ Skin reactions P450 and drugs

[Guest guest]

Matt:

Looks to me like alot of skin reactions to drugs are related to how

we metabolize those drugs (P450 expression is not exclusive to the

liver it seems).

It's looing like t P450 profile should be done on anyone who's going

to take alot of drugs (antibiotics in particular).

This is interesting:

J Pharmacol Exp Ther. 2006 Dec;319(3):1162-71. Epub 2006 Sep 19.

Differentiation-specific factors modulate epidermal CYP1-4 gene

expression in human skin in response to retinoic acid and classic

aryl hydrocarbon receptor ligands.

Du L, Neis MM, Ladd PA, Keeney DS.

Department of Medicine, Vanderbilt University School of Medicine, 607

Light Hall (0146), Nashville, TN 37232-0146, USA.

Human epidermal keratinocytes express subsets of cytochromes P450

(P450) (CYP gene products) that are strongly up-regulated, not

regulated, or down-regulated by differentiation-specific factors. We

investigated how drug exposure affects epidermal expression of CYP1-4

genes, which encode many drug-metabolizing P450s. Real-time

polymerase chain reaction (PCR) assays measured CYP1-4 mRNA levels in

epidermal keratinocytes differentiated in vitro in the presence of

drug or vehicle for 6 days. We confirmed the spinous phenotype at day

6 by changes in cellular morphology and upregulation of cytokeratin

10 and transglutaminase (TGM)1 mRNA in the differentiating

keratinocytes. Effects of drug exposure depended on the influence of

differentiation-specific factors in controlling epidermal CYP1-4

expression. CYP2C18, 2C19, 2C9, 2W1, 3A4, and 4B1 are up-regulated by

cellular differentiation; mRNA levels for these CYP genes were

inhibited in differentiating keratinocytes exposed to retinoic acid

and aryl hydrocarbon receptor (AhR) ligands. These same drugs

effected <or=2-fold change or even augmented mRNA levels for CYP

genes that are not regulated by differentiation (CYP2S1, 2J2, 1B1,

1A1, 1A2, 2E1, and 2D6) and for CYP2U1, which is expressed at highest

levels in undifferentiated keratinocytes. The clinically relevant

drugs miconazole, dexamethasone, rifampicin, and dapsone had little

effect on CYP1-4 mRNA levels under assay conditions. The AhR ligand

2,3,7,8-tetrachlorodibenzo-p-dioxin also up-regulated keratinocyte

TGM1 mRNA in a concentration- and time-dependent manner. This effect

was blocked by the AhR antagonist resveratrol. These findings

implicate AhR-dependent up-regulation of TGM1 mRNA in differentiating

keratinocytes as one mechanism contributing toward chloracne in

humans exposed to toxic levels of dioxin.

PMID: 16985168 [PubMed - indexed for MEDLINE]