ZN/CU NUTRITION AND FREE RADICAL GENERATION IN LUNG

本项目旨在验证一个假设，即不正常摄入的 膳食锌和铜，导致血浆和组织锌：铜比值异常， 将导致肺维持足够的 防御活性自由基物种。 选择Zn和Cu 因为它们直接参与酶促反应， 使活性氧物质解毒。 铜和锌是必需的辅因子， 金属酶Cu-Zn超氧化物歧化酶是一种细胞溶质酶， 催化O2歧化为H2 O2。 Zn也稳定了结构 和细胞膜的功能，减少脂质过氧化和保护 蛋白质中不稳定的巯基。 饮食中的锌和铜 在生长的饮食中被操纵到不足和超正常水平 大鼠 该项目的具体目标是：（a）确定 由于饮食中锌和铜的摄入导致内源性自由基的产生，B） 为了定量肺中自由基诱导的氧化损伤， 受Zn/Cu状态的影响，c）评估对 Zn/Cu对外源性化学物质所致肺氧化损伤的影响 用诱导游离的化学品激发动物后的状态 自由基和肺病理学，d）阐明Zn/Cu 营养会影响自由基的产生， 肺中的氧化应激，和e）确定Zn/Cu的作用 负责代谢活化的酶系统的状态， 自由基物质的失活，即，异生物质代谢和 氧气防御系统 长期目标是确定 自由基的产生和自由基引起的损伤 肺和阐明的具体机制，自由基 肺中产生的毒素受动物营养状况的影响， 人类 该项目旨在提供有关饮食影响的数据， 锌和铜对肺解毒自由基的能力， zenobiotics. 这些数据可以用来进一步了解 正常人肺和患病人肺的功能。

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.