VITAMIN E/SELENIUM/OXIDATION/PULMONARY ARACHIDONIC ACID

这项研究的主要目的是阐明 维生素E和硒参与的性质 花生四烯酸（AA）的酶促氧化的调节 环氧合酶和脂氧合酶途径。 为了获得进一步 了解维生素E的确切机制， 硒依赖的抗氧化防御功能，03是 采用了一个模型氧化剂的调查， 氧化应激的生物化学和免疫学后果 E/Se缺乏。 要检验的假设是， 氧化应激，例如在E/Se缺乏状态中发现的氧化应激，可 干扰酶的活性以及产品的概况 AA级联。 这些AA代谢产物可能在 在氧化剂引起的肺损伤的病理生理学中的作用。 因此，我们建议研究O3暴露的影响， 在缺硒、缺硒或缺硒的大鼠中：1） 肺中脂质过氧化物和其他TBA反应产物的水平 血栓素A2-前列环素I2的状态 体内平衡; 3）形成的felandins，F2 α，E2和 D2和参与其生物合成的酶，在这种情况下， 谷胱甘肽S-转移酶; 4）白三烯和 参与其生物合成的酶，特别是5- 脂氧合酶和谷胱甘肽S-转移酶; 5）能力 肺的体外代谢花生四烯酸的潜力; AA依赖性脂质过氧化和共氧化 肺和肺泡的苯并芘-7，8-二氢二醇 巨噬细胞功能。 拟采用的研究方法 包括分光光度法和同位素分析， 酶活性测定，放射免疫测定，液体 闪烁光谱法、GC/MS、薄层和高压 分析的脂质色谱技术 三尖杉素和白三烯。 新的信息来源 从拟议的努力应该加深我们的理解 维生素E和硒在调节 环氧合酶和脂氧合酶途径。

The primary objective of the proposed research is to elucidate the nature of involvement of vitamin E and selenium in the modulation of enzymatic oxidation of arachidonic acid (AA) via the cyclooxygenase and lipoxygenase pathways. To gain further knowledge on the precise mechanism(s) of vitamin E and selenium-dependent antioxidant defense functions, 03 is employed an a model oxidant for the investigation of the biochemical and immunological consequences of oxidant stress under E/Se deficiency. The hypothesis to be tested is that an oxidant stress, such as that found in the E/Se deficient state, can perturb enzyme activities as well as the product profile of the AA cascade. These AA metabolites may play an important role in the pathophysiology of oxidant-induced lung damage. Accordingly, we propose to examine the effects of O3 exposure in rats under E deficiency, Se deficiency or both on: 1) the levels of lipid peroxides and other TBA reactive products in lung and blood; 2) the status of thromboxane A2-prostacyclin I2 homeostatis; 3) the formation of prostaglandins, F2 alpha, E2 and D2, and the enzymes involved in their biosynthesis, in this case, the glutathione S-transferases; 4) the leukotrienes and the enzymes involved in their biosynthesis, particularly the 5- lipoxygenase and the glutathione S-transferases; 5) the capacity of lung to metabolize arachidonic acid in vitro; 6) the potential for AA-dependent lipid peroxidation and cooxidation of benzopyrene-7, 8-dihydrodiol of lung and 7) pulmonary alveolar macrophage functions. The research methods to be employed include spectrophotometric and isotopic assays for the measurement of enzyme activities, radioimmunoassays, liquid scintillation spectrometry, GC/MS, thin-layer, and high pressure lipid-chromatographic techniques for the analysis of prostaglandins and leukotrienes. New information to be derived from the proposed effort should deepen our understanding of the role of vitamin E and selenium in modulation of the cyclooxygenase and lipooxygenase pathways.