Temporal changes in heart size, hematocrit and erythrocyte membrane protein in copper-deficient rats

Abstract

The temporal relationship between Cu depletion and the development of anemia, cardiac hypertrophy and altered erythrocyte membrane protein composition was investigated. Male, weanling Sprague-Dawley rats were fed diets containing either <1 μg Cu/g (CuD) or 5 μg Cu/g (CuA) and sampled at weekly intervals for 6 weeks. Within 2 weeks of dietary treatment, liver Cu concentration, cytochrome c oxidase activity and Cu, Zn-superoxide dismutase activity were significantly lower in rats fed CuD than in those fed CuA. Hearts from rats fed CuD exhibited poor Cu accretion from week 3 of dietary treatment onward. Plasma ceruloplasmin and Cu concentration remained lower in rats fed CuD than in those fed CuA throughout the 6 weeks of dietary treatment. Reduction of plasma Fe occurred in week 1, reduction of heart Fe in week 3 and increase of liver Fe in week 5 in CuD-fed rats. Anemia, characterized by lowered hematocrit and hemoglobin concentration and increased red cell distribution width, developed within 2 weeks in rats fed CuD. The abnormal appearance of a 170 kDa protein was not apparent in erythrocyte membranes of CuD-fed rats until after week 3 of dietary treatment. Cardiac hypertrophy of CuD-fed rats, as indicated by higher heart weights and heart weight/body weight ratios, appeared at week 3 of dietary treatment. The relatively smaller increases in per cent heart water did not occur until week 6 of Cu deficiency. We conclude from the above temporal changes that: changes in blood iron status in CuD-fed rats parallel hematocrit-hemoglobin changes and may therefore be related to them; the changes in erythrocyte membrane protein that we observed are not likely to be the cause of anemia; anemia of Cu deficiency precedes cardiac hypertrophy and therefore could play a role in its development; changes in enzymes which could make Cu-deficient animals vulnerable to oxidative damage occur soon enough to be a possible cause of either anemia or cardiac hypertrophy.