Modification of anti-inflammatory drug effectiveness by ambient lipid peroxides.
When the steady-state concentrations of peroxide in prostaglandin H synthase assay systems was lowered by added glutathione peroxidase, several agents (meclofenamic acid, mefenamic acid, acetamidophenol and phenylbutazone) became more potent inhibitors of the prostaglandin-forming cyclooxygenase reaction. Paradoxically, these agents stimulated oxygen incorporation in the absence of added peroxidase. On the other hand, dithiothreitol, ibuprofen, flurbiprofen and indomethacin all inhibited the reaction in a dose-dependent manner, and their inhibitory potencies were unaffected by the action of glutathione peroxidase. Aspirin, dl-gamma-tocopherol and salicylic acid were not inhibitory (without preincubation) under the assay conditions employed in this study. The findings demonstrate that the potencies of some anti-inflammatory agents may be diminished by high local peroxide concentrations.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D008054:Lipid Peroxides; D011451:Prostaglandin-Endoperoxide Synthases