MARGINAL COPPER INTAKE EFFECTS--SOD & LIPID PEROXIDATION

边际铜摄入量的影响

• 批准号: 3463245
• 负责人: ROBERT A DISILVESTRO
• 金额: $ 9.65万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3463245
• 关键词: cancer risk; copper; dietary trace element; enzyme mechanism; hypocupremia; laboratory rat; lipid peroxides; liver metabolism; metalloenzyme; nutrition related tag; pathogenic diet; stress; superoxide dismutase

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.

许多美国人的铜摄入量低于推荐的饮食量。 然而，这种边际铜摄入量的后果仍有待进一步研究。 测定 拟议的项目将检验这一假设， 大鼠体内的铜状态可产生足够低的肝脏活性 铜锌超氧化物歧化酶（SOD）浓度高， 脂质过氧化作用。 Cu-Zn SOD清除超氧自由基， 导致脂质过氧化，这一过程被认为是导致许多疾病的原因 以及包括癌症在内的伤害。 将对以下方面的影响进行研究： 边缘铜状态单独，并结合3个应力状态， 可降低大鼠肝脏Cu-Zn SOD活性（边缘锌状态， 炎症和链脲霉素诱导的糖尿病）。 老鼠也会被喂食 边际铜水平（2.5 ppm Cu），或出于比较目的， 认为水平足够（6.0 ppm）或极低（0.2 ppm）。 在 每个饮食组的一些大鼠，加上或减去应激状态，脂质 过氧化作用将被CC 14刺激。 这种药剂经常被用来模仿 许多过氧化物生产状态，可能发生在人类。 饮食将是 雄性、断奶大鼠给药5或15周，或成年大鼠给药5周 大鼠 各方案大鼠均表现出不同程度的抗脂作用 过氧化作用比其他方案中的大鼠。 由于脂质过氧化 可以发生在一个以上的亚细胞部位，并引起几种类型的 损害，这一过程将通过一些测量进行评估。 实例包括共轭二烯积累和苯肼反应性 不饱和脂肪酸水平。 后者被认为与风险有关 癌症的发展。 总而言之，这个项目将研究一个普通的人， 营养问题，边缘铜状态，肝脏Cu-Zn SOD 活动和脂质过氧化，2个生物学参数，可能 广泛的健康影响。