Evidence of peroxidative damage to the erythrocyte membrane in iron deficiency.

The mechanism responsible for reduced red blood cell (RBC) survival in iron deficient infants or animals is unknown. To investigate the possible role of membrane peroxidation in iron-deficiency anemia, we studied RBC membrane lipids and proteins of rats fed iron-deficient (2 ppm Fe) and control (50 ppm Fe) diets between 21 and 41 days of age. Thin-layer chromatography of lipids showed that iron-deficient rats' RBC contained a novel phospholipid (1.9% of the total phospholipid) which moved between phosphatidylserine and phosphatidylethanolamine. Detailed studies showed that this PL is a Shiff's base adduct of phosphatidylserine, phosphatidyl-ethanolamine, and malonyldialdehyde, an end product of lipid peroxidation. Polyacrylamide gel electrophoresis of RBC proteins of iron-deficient rats also showed presence of high molecular protein complexes similar to that formed in in vitro malonyldialdehyde-treated RBC. To examine the role of such membrane cross-linking on in vivo RBC survival, we have studied survival of in vitro malonyldialdehyde-treated RBC in rabbits, 51Cr-T 1/2 of 5 microM malonyldialdehyde-treated RBC, which contained about the same amount of phospholipid/malonyldialdehyde adducts, was reduced to 6 days as compared to 11 days of sham-treated RBC. The in vitro study suggests that peroxidative damage results in significant reduction in RBC T 1/2 and may be analogous to decreased RBC survival in iron-deficient infants and animals.