Inhibition of erythema induced by pro-inflammatory esters of 12-deoxyphorbol.
The pro-inflammatory tigliane esters 12-deoxyphorbolphenylacetate (12-DOPPA) and 12-deoxyphorbolphenylacetate-20-acetate (12-DOPPAA) at a dose of 0.1 microgram induced erythema in the mouse ear. Observations of ear redness were made both two and four hours after application. Indomethacin was only partly successful as an antagonist since 10% inhibition of 12-DOPPA and no inhibition of 12-DOPPAA induced erythema was produced four hours after application. The free radical scavengers, phenol, thioanisole and sodium benzoate all produced less than 30% inhibition of 12-DOPPA induced erythema and less than 15% inhibition of 12-DOPPAA, whereas aminopyrine produced 70% and 25% inhibition of 12-DOPPA and 12-DOPPAA respectively. The fact that free radical scavengers (with the exception of aminopyrine) and indomethacin, failed to markedly change the mouse ear reaction to 12-deoxyphorbol esters, indicated that this erythema is not entirely mediated via cyclooxygenase products. Mepyramine and cyproheptadine also failed to inhibit the erythema, whereas hydrocortisone produced a 55% inhibition of the 12-DOPPA and a 20% inhibition of the 12-DOPPAA reaction. The membrane stabilising agents trifluoperazine, promethazine, imipramine and desmethylimipramine were the most successful compounds used in inhibiting both 12-DOPPA and 12-DOPPAA induced erythema. In addition propranolol, which inhibits stimulus activation of phospholipase A2, produced 70% and 55% inhibition of the reaction of mice ears to 12-DOPPA and 12-DOPPAA.
D000818:Animals; D004890:Erythema / Q000139:chemically induced*; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000037:antagonists & inhibitors; D051379:Mice; D010703:Phorbol Esters / Q000037:antagonists & inhibitors
D006634:Histamine H1 Antagonists; D007509:Irritants; D010703:Phorbol Esters; C029705:12-deoxyphorbolphenylacetate-20-acetate; C029704:12-deoxyphorbolphenylacetate; D006854:Hydrocortisone; D007213:Indomethacin