Modification of anti-inflammatory drug effectiveness by ambient lipid peroxides

Biochem Pharmacol. 1982 Oct 15;31(20):3307-11. doi: 10.1016/0006-2952(82)90565-2.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Arachidonic Acids / pharmacology
  • Drug Interactions
  • In Vitro Techniques
  • Lipid Peroxides / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats

Substances

  • Anti-Inflammatory Agents
  • Arachidonic Acids
  • Lipid Peroxides
  • Prostaglandin-Endoperoxide Synthases