Anthralin inhibits elevated levels of thioredoxin reductase in psoriasis. A new mode of action for this drug.

Membrane-associated thioredoxin reductase (TR) activity has been measured in 3-mm punch biopsy specimens from psoriatic and uninvolved skin in eight patients with chronic plaque-type psoriasis vulgaris. The mean specific activity for this free radical reducing enzyme in psoriatic vs uninvolved skin was 28.5 +/- 8.0 U vs 16.8 +/- 4.25 U. Because TR contains two reactive thiolate groups at its active site, this enzyme reacts with anthralin to form a covalent anthralin-TR complex causing irreversible enzyme deactivation. This mode of action for anthralin was confirmed by using pure TR from Escherichia coli. Keratinocyte cell cultures, grown from normal and psoriatic skin of one donor, revealed 24% and 42% inhibition of cell surface TR activity, respectively, in the presence of 2 X 10(-5)M anthralin. Time-dependent topical application of anthralin on guinea pig skin gave 70% inhibition of TR with concentrations of 0.25% to 1.0% after 24 hours in open and occlusive applications of the drug. Short contact with 1% anthralin showed 70% inhibition after 120 minutes.