Many Americans consume below recommended amounts of dietary copper. However, the consequences of such marginal copper intake remain to be determined. The proposed project would test the hypothesis that marginal copper status in rats can produce low enough hepatic activity concentrations of Cu-Zn superoxide dismutase (SOD) to cause high degrees of lipid peroxidation. Cu-Zn SOD eliminates superoxide radicals which can causes lipid peroxidation, process believed to contribute to many disease and injuries including cancer. Studies will be conducted on the effects of marginal copper status alone, and combined with 1 of 3 stress states which can reduce rat liver Cu-Zn SOD activities (marginal zinc status, inflammation and streptozotocin-induced diabetes). Rats will be fed either marginal copper levels (2.5 ppm Cu) or, for comparison purposes, fed copper level considered adequate (6.0 ppm) or extremely deficient (0.2 ppm). In some rats from each diet group, plus or minus the stress states, lipid peroxidation will be stimulated by CC14. This agent is often used to mimic many peroxide production states which could occur in humans. Diets will be given for 5 or 15 weeks to male, weanling rats, or for 5 weeks to adult rats. Rats in each protocol could show more or less resistance to lipid peroxidation than rats in the other protocols. Since lipid peroxidation can occur in more than one subcellular site and cause several types of damage, this process will be assessed by a number of measurements. Examples include conjugated diene accumulation and phenylhydrazine-reactive unsaturated fatty acids levels. The latter is considered relevant to risk of cancer development. In summary, this project would study a common human nutritional problem, marginal copper status, in terms of liver Cu-Zn SOD activities and lipid peroxidation, 2 biological parameters with potentially wide ranging health implications.
| DiSilvestro, R A; Carlson, G P (1994) Effects of mild zinc deficiency, plus or minus acute phase response, on CCl4 hepatotoxicity. Free Radic Biol Med 16:57-61 |
| Yang, F L; David, E A; DiSilvestro, R A (1993) Neonatal rat liver contains low concentrations of Cu-Zn superoxide dismutase protein and mRNA. Biochim Biophys Acta 1156:232-4 |
| DiSilvestro, R A; Medeiros, D M (1992) Low and marginal copper intake by postweanling rats: effects on copper status and resistance to carbon tetrachloride hepatotoxicity. Metabolism 41:1122-4 |
| DiSilvestro, R A; Carlson, G P (1991) Effects of moderate copper deficiency on carbon tetrachloride-induced hepatotoxicity in rats. Proc Soc Exp Biol Med 197:32-5 |
| DiSilvestro, R A; Marten, J T (1990) Effects of inflammation and copper intake on rat liver and erythrocyte Cu-Zn superoxide dismutase activity levels. J Nutr 120:1223-7 |
