Relation Between Zinc and Iron and Peroxidation of Lipids in Liver Homogenate in CaEDTA-Treated Rats

Document Type

Article

Publication Date

1-1-1974

Description

Rats were administered CaEDTA at 6 mmoles/kg/24 hr either by continuous iv infusion for various periods of time up to 48 hr or by ip injection (twice daily) for 14 days. The urinary excretion pattern for zinc, iron, and copper was compared with the content of these metals in the liver. The formation of malondialdehyde (MA) and the profile of total fatty acids was studied in the liver as an index of the capacity to peroxidize unsaturated fatty acid. The urinary excretion of zinc in rats infused iv with CaEDTA reached a maximum within 3 hr, then steadily declined. By contrast, the urinary excretion of iron continuously increased during the period of infusion. Still, total zinc excretion exceeded iron excretion 10-fold over the 48-hr period. A significant decrease in the zinc content of liver occurred 2 hr after the start of infusion and was only half that of controls after 48-hr infusion. The content of iron in the liver did not change. A significant increase of copper occurred in the liver in spite of the fact that enhanced urinary excretion could account for 15% depletion of total body stores. The formation of MA by the liver was significantly enhanced in rats infused with CaEDTA for 2 hr; infusion with CaEDTA for 48 hr resulted in abolishing the capacity of the liver to produce MA. Addition of iron to liver homogenate reestablished its capacity to produce MA. A similar pattern of metal content in the liver was measured for rats chronically treated with CaEDTA; zinc significantly decreased with no change in iron. However, the capacity of the liver to produce MA was enhanced. These data, supported by changes in the profile of fatty acids, favor the view that a decrease in zinc content with no change in biologically active iron content enhances lipid peroxidation by the liver. Chelation of iron in the liver with time during the constant iv infusion of CaEDTA, presumably through the formation of ternary iron complexes in situ, prevents lipid peroxidation.

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