Effect of Topically Applied Cyclooxygenase-2-Selective Inhibitors on Arachidonic Acid- and Tetradecanoylphorbol Acetate-Induced Dermal Inflammation in the Mouse |
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Authors: | Violant Puigneró Josep Queralt |
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Institution: | (1) Unitat de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, c/Joan XXIII, s/n, 08028- Barcelona, Spain |
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Abstract: | The topical effects of cyclooxygenase-2 (COX-2)-selective inhibitors, flosulide (CGP 28238), L-745,337 and SC-57,666 were examined in AA- and TPA-induced ear dermal inflammation in the mouse. The doses that caused 50% inhibition in AA edema (ED50) were 2.4, 0.45 and 0.35 mg/ear for flosulide, L-745,337 and SC-57,666, respectively. The respective ED50s
in TPA-edema were 1, 0.45 and 0.14. Indomethacin and zileuton showed higher activity than the COX-2-selective inhibitors in both models. Flosulide and L-745,337 inhibited the AA-induced increase in 6-keto-PGF1 , while SC-57,666 was inactive. 80% inhibition was seen with indomethacin while zileuton had no effect. COX-2 selective inhibitors and indomethacin had no effect on LTB4 levels, while zileuton produced a 50% inhibition. The TPA-induced increase in 6-keto-PGF1 was greatly inhibited by all COX-2 inhibitors while LTB4was potentiated by both flosulide and L-745,337. Indomethacin inhibited 6-keto-PGF1 and zileuton reduced 6-keto-PGF and strongly reduced LTB4. The neutrophil influx induced by AA was lower than that of TPA. Myeloperoxidase (MPO) levels were lowered by flosulide and L-745,337 but not by SC-57,666. TPA-induced MPO increase was decreased by all COX-2 inhibitors. Indomethacin and zileuton had similar effect on AA and TPA-induced increase in MPO. The results indicate that COX-2-selective inhibitors showed lower topical anti-inflammatory activity than indomethacin or zileuton. |
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