Depletion of hepatic antioxidants during granulomatous inflammation in the rat and local anti-inflammatory effects of free radical scavengers.
Changes in hepatic oxidative events have been studied during extrahepatic granulomatous inflammation in the rat, together with the local anti-inflammatory effects of scavengers of reactive oxygen species. During remote localized inflammation in the rat, we observed increased hepatic lipid peroxidation and reduced hepatic levels of protecting substances such as ascorbic acid, catalase and reduced glutathione, the specific substrate for the peroxide-metabolizing enzyme, glutathione peroxidase. The levels of superoxide dismutase did not alter significantly during the period of investigation (7 days). The half-life of aminopyrine was longer in rats with a stronger inflammatory response. In addition, catalase and the anti-oxidants, alpha-tocopherol and propyl gallate, inhibited granuloma development on local injection during the acute phase inflammation. Superoxide dismutase alone was devoid of anti-inflammatory effects, but markedly enhanced the effect of catalase. Scavengers of hydroxyl radicals and of singlet oxygen failed to display anti-inflammatory activity. The results indicate that peroxides may act as mediators of inflammation and that increased lipid peroxidation is not limited to the site of inflammation.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants; D001205:Ascorbic Acid; D002374:Catalase / Q000378:metabolism; D005609:Free Radicals; D005978:Glutathione; D006099:Granuloma / Q000188:drug therapy / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde; D011435:Propyl Gallate / Q000627:therapeutic use; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D014810:Vitamin E / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005609:Free Radicals; D014810:Vitamin E; D008315:Malondialdehyde; D011435:Propyl Gallate; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid