ZN/CU NUTRITION AND FREE RADICAL GENERATION IN LUNG

这个项目旨在检验这样一种假设，即异常摄入 饮食中的锌和铜，导致血浆和组织锌铜比值异常， 会导致肺维持充足的能力被破坏 对活性自由基物种的防御。选择锌和铜 因为它们直接参与了酶促反应 使活性氧物种解毒。铜和锌是人体必需的辅因子 金属酶铜锌超氧化物歧化酶，一种胞浆酶 催化O2歧化为双氧水。锌还能稳定结构 和细胞膜的功能，减少脂质过氧化，保护 蛋白质中不稳定的巯基。膳食中的锌和铜将是 在生长的饮食中被控制到不足和超常水平的 老鼠。该项目的具体目标是a)建立差异 由于饮食中锌和铜的摄入量导致内源性自由基的产生，b) 对自由基致肺组织氧化损伤的定量研究 受锌/铜状态的影响，c)评估易感性 锌/铜对异物致肺组织氧化损伤的影响 在用化学物质刺激动物后的状态 自由基与肺病理，d)阐明锌/铜的作用机制 营养影响自由基的产生并改变其易感性 肺组织中的氧化应激，以及e)确定锌/铜的影响 负责代谢激活和代谢的酶系统的研究现状 使自由基物种失活，即异种代谢和 氧气防御系统。长期目标是确定效果 营养对自由基生成和自由基损伤的影响 并阐明自由基致肺损伤的具体机制。 在肺中产生的物质受到动物营养状况的影响 人类。本项目旨在提供有关饮食影响的数据。 锌、铜对肺组织清除自由基能力的影响 有生菌。然后这些数据可以用来加深我们对 正常人和患病人肺的功能。

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.