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Effect of topically applied cyclooxygenase-2-selective inhibitors on arachidonic acid- and tetradecanoylphorbol acetate-induced dermal inflammation in the mouse.

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 alpha, 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 alpha was greatly inhibited by all COX-2 inhibitors while LTB4 was potentiated by both flosulide and L-745,337. Indomethacin inhibited 6-keto-PGF1 alpha and zileuton reduced 6-keto-PGF alpha 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.
AuthorsV Puigneró, J Queralt
JournalInflammation (Inflammation) Vol. 21 Issue 4 Pg. 431-42 (Aug 1997) ISSN: 0360-3997 [Print] United States
PMID9276765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Eicosanoids
  • Isoenzymes
  • Arachidonic Acid
  • Peroxidase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Acetylglucosaminidase
  • Tetradecanoylphorbol Acetate
Topics
  • Acetylglucosaminidase (metabolism)
  • Administration, Topical
  • Animals
  • Arachidonic Acid
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors (pharmacology)
  • Drug Eruptions (metabolism, pathology)
  • Eicosanoids (biosynthesis)
  • Isoenzymes (metabolism)
  • Male
  • Mice
  • Mice, Inbred Strains
  • Peroxidase (metabolism)
  • Prostaglandin-Endoperoxide Synthases (metabolism)
  • Tetradecanoylphorbol Acetate

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