This project is designed to test the hypothesis that abnormal intake of dietary Zn and Cu which results in abnormal plasma and tissue Zn:Cu ratios, will result in a disruption of the ability of the lung to maintain adequate defense against reactive free radical species. Zn and Cu are chosen because they are directly involved in the enzymatic reactions for detoxifying the active oxygen species. Cu and Zn are required cofactors in the metalloenzyme Cu-Zn superoxide dismutase, a cytosolic enzyme which catalyzes the dismutation of O2 to H2O2. Zn also stabilizes the structure and function of cell membrane, decreases lipid peroxidation and protects labile sulfhydryl groups in proteins. Dietary Zn and Cu will be manipulated to both deficient and supranormal levels in the diet of growing rat.
The specific aims of the project are a) to establish the differences due to dietary Zn and Cu intake in endogenous free radical production, b) to quantitate free radical-induced oxidative damage in the lung as influenced by the Zn/Cu status, c) to assess the susceptibility to oxidative damage induced by xenobiotics in the lung as affected by Zn/Cu status after challenging the animal with chemicals which induce free radicals and lung pathology, d) to elucidate the mechanisms by which Zn/Cu nutrition affects free radical production and alters the susceptibility to oxidative stress in the lung, and e) to determine the effect of Zn/Cu status on the enzymatic systems responsible for metabolic activation and deactivation of free radical species, i.e., xenobiotic metabolism and oxygen defense systems. The long term objective is to determine the effect of nutrition on free radical production and free radical-induced damage in the lung and to elucidate the specific mechanisms by which free radicals generated in the lung are influenced by nutritional status of animals and humans. This project is intended to provide data on the effect of dietary Zn and Cu on the ability of the lung to detoxify free radicals and zenobiotics. These data can then be used to further our understanding of the functions of the normal and diseased human lung.
| Bray, T M; Bettger, W J (1990) The physiological role of zinc as an antioxidant. Free Radic Biol Med 8:281-91 |
| Taylor, C G; Towner, R A; Janzen, E G et al. (1990) MRI detection of hyperoxia-induced lung edema in Zn-deficient rats. Free Radic Biol Med 9:229-33 |
| Hammermueller, J D; Bray, T M; Bettger, W J (1987) Effect of zinc and copper deficiency on microsomal NADPH-dependent active oxygen generation in rat lung and liver. J Nutr 117:894-901 |
| Bray, T M; Kubow, S; Bettger, W J (1986) Effect of dietary zinc on endogenous free radical production in rat lung microsomes. J Nutr 116:1054-60 |
