Effects of glutathione depletion, chelation and diuresis on iron nitrilotriacetate-induced lipid peroxidation in rats and mice.
1. Rats and mice dosed with iron nitrilotriacetate (FeNTA) i.p. (2-12 mg Fe/kg) showed evidence of lipid peroxidation as indicated by increased exhalation of ethane and increased malondialdehyde formation in liver and kidney. 2. Buthionine sulphoximine (BSO) administered i.p. to rats and mice decreased the total glutathione (GSH) content of liver and kidney. When the rodents were pretreated i.p. with BSO prior to injection of FeNTA the increases in ethane exhalation, and in liver and kidney malondialdehyde production, were greater than with FeNTA alone, and the total GSH of liver and kidney were decreased. 3. Diuresis produced by i.p. administration of furosemide to mice substantially decreased the ethane exhalation resulting from FeNTA administration, had a lowering effect on kidney MDA, but had no significant effect on liver MDA production. 4. Similarly, desferrioxamine beta-mesylate administered i.p. to mice markedly decreased the ethane exhalation and kidney MDA production resulting from FeNTA administration.
Preece
N E
NE
Toxicology Unit, School of Pharmacy, London University, UK.
Evans
P F
PF
King
L J
LJ
Parke
D V
DV
D000818:Animals; D019328:Buthionine Sulfoximine; D002614:Chelating Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D005290:Ferric Compounds / Q000633:toxicity*; D005665:Furosemide / Q000494:pharmacology; D005978:Glutathione / Q000172:deficiency*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D002614:Chelating Agents; D004232:Diuretics; D005290:Ferric Compounds; D008717:Methionine Sulfoximine; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D005665:Furosemide; D005978:Glutathione; D003676:Deferoxamine; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate