ANEMIA IN COPPER-DEFICIENT RATS - ROLE OF ALTERATIONS IN ERYTHROCYTE-MEMBRANE FLUIDITY AND OXIDATIVE DAMAGE

This study was designed to make precise the nature and the mechanism o f the anemia induced by dietary copper (Cu) deficiency. Male Wistar ra ts were pair fed from weanling for 6 wk either a Cu-deficient or a con trol diet. The reduced red blood cell (RBC) Cr-51 survival indicates a n increased destruction of RBC during Cu deficiency. 1,6-Diphenyl-1,3, 5-hexatriene fluorescence polarization studies revealed an increase in the fluidity of erythrocyte membranes from deficient rats. The reduce d cholesterol-to-phospholipid ratio was consistent with the increased fluidity. Other results indicate an increased vulnerability of RBC to hemolysis in dilute hydrogen peroxide and an increased formation of li pid peroxidation products. Before exposure to free radical stress, ele ctron spin resonance studies in intact RBC revealed decreased correlat ion time of 16-doxyl-stearic acid, confirming a more fluid membrane in RBC from Cu-deficient rats. After in vitro peroxidation, RBC from Cu- deficient rats showed a more ordered state of membrane lipids compared with controls. Together, these studies demonstrate the hemolytic natu re of the anemia. The shortened survival of erythrocytes apparently re sults from changes in membrane fluidity and enhanced susceptibility to peroxidation.