Characteristics and modulation of dithranol (anthralin)-induced skin irritation in the mouse ear model.

Dithranol-induced skin irritation and the modulatory effects of different pharmacological agents were studied using the mouse ear model. A single topical application of dithranol caused a dose-dependent skin irritation which resulted in delayed swelling of the mouse ear with two separate peak responses, 1-2 and 6-10 days after application. The irritation was most effectively and persistently inhibited by topical treatment with corticosteroids, the free radical scavenger DL-alpha-tocopherol (DLAT) and the serotonin antagonist metergoline. The effect of corticosteroids, however, was slightly diminished during the second peak irritation. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), the dual lipoxygenase and cyclo-oxygenase inhibitor tolfenamic acid and the cyclo-oxygenase inhibitor indomethacin as well as trifluoperazine retained their inhibitory activity. Of these compounds, indomethacin was active only during the first irritation peak, NDGA during both peaks and trifluoperazine principally during the second peak. Retinoic acid did not inhibit the ear swelling. The results confirm and extend the observations that the formation of free radicals is essential for dithranol inflammation. The inflammation can also be suppressed by inhibiting the formation of arachidonic acid or its pro-inflammatory metabolites.