In vivo formation of hydroxyl radicals following intragastric administration of ferrous salt in rats.
Accidental poisoning by oral iron preparations is a serious problem in young children. We investigated the formation of hydroxyl radicals (.OH) in rats after intragastric instillation of ferrous sulfate. .OH was detected via its reaction with intragastrically administered 2-keto-4-methylthiobutyrate to generate ethylene gas. Ascorbic acid is typically present in oral iron preparations in order to facilitate absorption by maintaining iron in the reduced state. However, ascorbate possesses two properties that can affect .OH, recycling of oxidized iron to the ferrous state augments .OH production, while ascorbate in high concentration scavenges .OH. In experiments conducted in vitro, both actions were evident, depending upon the concentration of ascorbate. In parallel experiments conducted in vivo, the scavenging action of ascorbate was more prominent. Experiments in vitro with .OH-scavengers (dimethylsulfoxide, ethanol) and with the enzyme, catalase, confirmed both the presence of .OH and its dependence upon generated hydrogen peroxide during the oxidation of ferrous salt by molecular oxygen. Hydroxyl radicals (and/or reactive higher oxidation states of iron) may play a role in tissue damage after accidental overdose of oral iron.
Kang
J O
JO
Department of Neurology, Graduate School of Biomedical Sciences, Mount Sinai School of Medicine, New York, NY 10029.
Slivka
A
A
Slater
G
G
Cohen
G
G
D000284:Administration, Oral; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005030:Ethylenes / Q000378:metabolism; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000506:poisoning*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains
D005030:Ethylenes; D005296:Ferrous Compounds; D006878:Hydroxides; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D000431:Ethanol; C036216:ethylene; D006861:Hydrogen Peroxide; D002374:Catalase; D001205:Ascorbic Acid; D004121:Dimethyl Sulfoxide