Oxidant stress during inflammation: anti-inflammatory effects of antioxidants.

Local oxidative changes have been investigated during granulomatous inflammation in the rat. Lipid peroxidation occurred independently of the prostaglandin biosynthetic pathways in the kaolin granuloma pouch model. Elevated levels of malonaldehyde, The monitor of lipid peroxidation, were found in the plasma and livers of rats with a remote localized inflammation. The hepatic antioxidant capacity of these rats was markedly reduced, while aminopyrine metabolism was impaired, as reflected by the increased half-life of this drug. The aminopyrine half-life was longer in rats with a stronger inflammatory response. Local administration of free radical scavengers and antioxidants inhibited granuloma formation depending on the type of scavenger used. Thus scavengers of superoxide and hydroxyl radicals were ineffective as anti-inflammatory agents, whereas a scavenger of hydrogen peroxide and two lipid antioxidants markedly inhibited granuloma formation. The results indicate that several states of reduced oxygen and lipid peroxides are involved in the inflammatory response, and that the oxidative events are not limited to the inflamed site.