Radical scavenging as the mechanism for stimulation of prostaglandin cyclooxygenase and depression of inflammation by lipoic acid and sodium iodide.
Certain radical-trapping reducing agents have been shown to stimulate prostaglandin biosynthesis in vitro (1--6) and to depress phorbol myristate acetate-induced mouse ear edema (16). The increased prostaglandin synthesis resulted from influences on the cyclooxygenase. To ascertain whether these alterations were due to direct interaction with the enzyme or to indirect scavenging of the oxidant released during PGG2 reduction, we report the effects of lipoic acid and sodium iodide. Both of these agents stimulated the enzymatic oxygenation of arachidonic acid, increased the reduction of PGG2 to PGH2, quenched the EPR signal induced by arachidonic acid and depressed mouse ear edema. In addition to discovering two unusual antiinflammatory agents, we have confirmed that materials with entirely different structures can have identical effects on the cyclooxygenase, suggesting indirect stimulation of this enzyme due to trapping of the oxidant.
D000818:Animals; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids / Q000378:metabolism*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D007454:Iodides / Q000627:therapeutic use*; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000096:biosynthesis*; D012974:Sodium Iodide / Q000627:therapeutic use*; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors; D008063:Thioctic Acid / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D007454:Iodides; D011453:Prostaglandins; D008063:Thioctic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D012974:Sodium Iodide; D013755:Tetradecanoylphorbol Acetate