Effects of prostaglandin antagonist phloretin derivatives on mouse ear edema induced with different skin irritants

Edema was induced in one ear of male mice of the CFLP strain with solutions of different skin irritants (croton oil 10 mu L/35 mu g, dithranol 20 mu L/30 mu g, capsaicin 10 mu L/40 mu g or arachidonic acid to 10 mu L/2 mg per ear). Edema, determined by the edema-disk gravimetric technique, was inhibited in a dose-dependent manner by the intraperitoneally administered prostaglandin antagonists polyphloretin phosphate (PPP) or di-4-phloretin phosphate (DPP). With croton oil-induced mouse ear edema, DPP 10 mg/kg caused a 38% inhibition, PPP 25 mg/kg a 33% inhibition. With dithranol-induced edema DPP 0.5 mg/kg caused a 57% inhibition, while PPP 25 mg/kg was needed to exert a similar effect. Doses of DPP and PPP needed to cause a >40% inhibition of edema were 10 mg/kg and 25 mg/kg, respectively for capsaicin, and 25 mg/kg and 200 mg/kg for arachidonic acid. The inhibition of the ear edema by the phloretin derivatives was: dithranol > croton oil > capsaicin > arachidonic acid. This probably reflects the different contributions of prostaglandins to the inflammation.