The induction of autoxidative tissue damage by iron nitrilotriacetate in rats and mice.
Iron nitrilotriacetate (FeNTA) is a potent initiator of lipid peroxidation, and, when injected intraperitoneally into mice, it greatly increased ethane and pentane exhalation within 30 min. The time course and dose-response of the exhalation of ethane were studied and compared with the increase in tissue malondialdehyde (MDA) production. Production of MDA was greater in mouse kidney than liver and correlated better with the exhalation of ethane. In rats FeNTA also increased ethane exhalation and MDA, but the rat was less susceptible than the mouse to FeNTA toxicity. MDA production was greater in rat liver than kidney and both correlated well with ethane exhalation (r = 0.97 and 0.98, respectively). Renal proximal tubular damage was observed histologically 35 min after mice were given FeNTA, but in rats the lesion appeared 24 hr after dosage. Histopathological assessment of kidney damage at these times showed fair correlation with ethane exhalation in mice (r = 0.73) and rats (r = 0.62), respectively. Activities of kidney brush-border marker enzymes were decreased in mice, 35 min after FeNTA administration, and showed a similar trend in rats. Some rats also showed periportal necrosis of the liver, 24 hr after FeNTA administration. The very rapid onset of autoxidative damage suggests that FeNTA itself is the causative agent rather than subsequently formed, less reactive complexes, such as transferrin. The site of damage in the kidney tubule is consistent with the region of concentration of filtered FeNTA. It is suggested that FeNTA supports the formation of superoxide ion from dissolved oxygen and may be responsible for the subsequent formation of hydroxyl radical which initiates lipid peroxidation. The species difference between rat and mouse may be due to the greater resistance of the rat kidney to FeNTA-induced autoxidative damage.
Preece
N E
NE
Department of Biochemistry, University of Surrey, Guildford, United Kingdom.
Evans
P F
PF
Howarth
J A
JA
King
L J
LJ
Parke
D V
DV
D000473:Alkanes / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism
D000473:Alkanes; D005290:Ferric Compounds; D008054:Lipid Peroxides; D013481:Superoxides; D008315:Malondialdehyde; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate