Lipid peroxidation and tissue injury by ferric citrate in paraquat-intoxicated mice.
To determine whether iron toxicity is caused by iron-catalyzed radical production, the in vivo effect of ferric citrate was studied in paraquat-intoxicated mice. Intraperitoneally injected Fe3+-citrate complex was distributed mainly in the liver and kidney, and promoted lipid peroxidation, as measured by expiratory ethane in both normal and paraquat-intoxicated mice. Plasma glutamic-oxaloacetic transaminase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1) activity increased significantly only in paraquat and Fe3+-citrate-injected mice (PFe group). The rate of ethane production increased prior to the elevation of plasma glutamic-oxaloacetic transaminase levels, and was greater in the PFe group than in the mice, that were injected Fe3+-citrate alone. Pretreatment of animals with desferrioxamine mesylate inhibited both ethane production and elevation of plasma glutamic-oxaloacetic transaminase levels in the PFe group. Administration of 100% oxygen or glucose, which is expected to increase cellular NADPH, to the PFe group further elevated the plasma glutamic-oxaloacetic transaminase level, but had little effect on ethane production, indicating that tissue injury occurs independently of lipid peroxidation. These results suggest that iron toxicity is due to radical production and that, although iron stimulated lipid peroxidation, it might not be the only cause of tissue injury.
Ogino
T
T
Department of Pathology, Okayama University Medical School, Japan.
Awai
M
M
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003676:Deferoxamine / Q000494:pharmacology; D004980:Ethane / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007501:Iron / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009249:NADP / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology / Q000633:toxicity*; D013481:Superoxides / Q000378:metabolism; D014018:Tissue Distribution; D014238:Trichloroacetic Acid
D005290:Ferric Compounds; D006878:Hydroxides; D008054:Lipid Peroxides; D013481:Superoxides; D017665:Hydroxyl Radical; D009249:NADP; D014238:Trichloroacetic Acid; C025314:ferric citrate; D007501:Iron; D001219:Aspartate Aminotransferases; D003676:Deferoxamine; D004980:Ethane; D010269:Paraquat; D010100:Oxygen