Antiatherogenic effects of zinc are associated with copper in iron-overloaded hypercholesterolemic rabbits

Fifty-four juvenile male New Zealand white rabbits were randomly allocated to 9 groups including chow-fed rabbits without mineral supplementation, HC diet fed rabbits without mineral supplementation, HC + Cu, HC + Zn, HC + FeO, HC + Cu + Zn, HC + FeO + Cu, HC + FeO + Zn, and HC + FeO + Cu + Zn. Feeding HC diet resulted in a significant (P < .001) increase in the serum cholesterol, TG, LDL, and very LDL except HDL when compared with chow-fed rabbits. The highest serum lipid profiles were observed in the FeO rabbits without copper or zinc supplementation. A modest decrease in serum thiobarbituric acid reactant substances in rabbits given the HC + Zn was accompanied by a significant (P < .05) increase in antioxidant enzymes activities excluding superoxide dismutase that was markedly lower than those given the HC + Cu (12.83 +/- 2.13 vs 16.00 +/- 2.23 U/mL serum). Supplementation with copper alone in both the FeO and the non-FeO rabbits significantly (P < .001) enhanced serum ceruloplasmin activity in comparison with other groups, but co-supplementation of copper plus zinc in the non-FeO rabbits did not significantly (P > .05) affect ceruloplasmin activity in comparison with those treated with unsupplemented regimens. A significant decrease was found in sudanophilia area of rabbits supplemented with zinc (62.36% +/- 3.55%) compared to those given the HC + FeO, the HC + FeO + Cu, and HC without mineral supplementation; however, no significant (P > .05) difference in animals given the HC + Cu, the HC + Cu + Zn, and the HC + FeO + Zn was observed. Based on these findings, it may be suggested that the antiatherogenic effects of zinc in presence of copper, on which there is overloading of iron, is reduced under hypercholesterolemia.