EFFECTS OF DIETARY FAT ON LIPID PEROXIDATIVE INJURY

我们将检验这样一种假设，即 对大鼠肝微粒体脂质过氧化反应的影响 用(n-3)家族的脂肪酸取代饮食中的(n-6)脂肪酸。 可能导致这种修改的两种机制是 首先，(n-3)脂肪酸的过氧化导致 在一组特定的氧化产物中，具有较少的 造成的伤害比来自(n-6)脂肪酸的那些更多；第二， (n-3)脂肪酸抑制磷脂酶A介导的脂肪酰化 释放并通过这样做改变脂质过氧化和 具体的产品是。第一种机制的合理性是 过氧化的特定有毒产物，包括4- 羟基壬烯醛，似乎需要(n-6)结构 队形。推导了第二种(磷脂酶)机理。 从大量的研究中可以看出 脂质过氧化事件与磷脂酶A升高之间的关系 以及关于膳食(n-3)脂肪酸抑制活性的报道 血小板中的脂肪酸释放。初步研究将确定脂质 从纯化的脂肪酸中提取的过氧化产物 超压层析法(OPLC)以及高效液相色谱仪和 在进行这些调查的同时，我们将评估 (n-6)和(n-6)和(n-2)过氧化产物的伤害效应 3)通过测量对酶活性的影响和脂肪酸的来源 溶酶体膜的完整性。这两种方法的比较效果 膳食(n-6)和(n-3)-脂肪酸对脂质过氧化的影响 通过喂食不同比例的大鼠定义的饮食进行评估 玉米油((n-6)浓缩)为薄荷油((n-3)浓缩)和 测定体外产生的微粒体过氧化产物 (通过还原的铁)和在体内(通过CCl4)。磷脂酶的作用 对微粒体脂过氧化产物的抑制作用(体外) 将被定义并与以下形成的定义进行比较 人工喂油大鼠微生物体的过氧化作用。效应 鱼油日粮对微粒体磷脂酶活性的影响 也将被定义。鉴于目前人们对饮食(n- 3)脂肪酸对于预防动脉粥样硬化很重要 了解这些化合物对血脂的影响 过氧化损伤，许多疾病的一个潜在方面 流程。

We will test the hypothesis that the damaging effects associated with rat liver microsomal lipid peroxidation may be modified by replacing dietary (n-6) fatty acids with those of the (n-3) family. Two mechanisms by which such modifications may result will be explored; first, that the perioxidation of (n-3) fatty acids results in a group of specific oxidative products with less of an ability to cause injury than those derived from (n-6) fatty acid; and second, that (n-3) fatty acids inhibit phospholipase A-mediated fatty acyl release and by so doing alter the course of lipid peroxidation and the specific productis. The rational for the first mechanism is that specific toxic products of peroxidation, including notedly 4- hydroxynonenal, appear to require the (n-6) structure for their formation. The second (phospholipase) mechanism was derived from numerous studies demonstrating a strong association between lipid peroxidative events and enhanced phospholipase A activities as well as reports that dietary (n-3) fatty acids inhibit fatty acid release in platelets. Initial studeis will identify lipid peroxidative products derived from purified fatty acids using Overpressure-Layer Chromatography (OPLC) as well as HPLC and GC/MS. In parallel with these investigations we will assess the injurious effects of purified peroxidation products of (n-6) and (n- 3) fatty acid origin by measuring effects on enzyme activities and on lysosomal membrane integrity. The comparative effects of dietary (n-6) and (n-3)-fatty acids on lipid peroxidation will be assessed by feeding rats defined diets with varying proportions of corn oil ((n-6)-enriched) to menhaden oil ((n-3)-enriched) and measuring microsomal peroxidation products generated in vitro (by reduced iron) and in vivo (by CCL4). Effects of phospholipase A inhibition on microsomal lipid peroxidative products (in vitro) will be defined and compared with those formed following peroxidation of microsomes from menhaden oil-fed rats. Effects of the menhaden oil diet on microsomal phospholipase activity will also be defined. In view of the current interest in dietary (n- 3) fatty acids for the prevention of atherosclerosis, it is important to understand the effects of these compounds on lipid peroxidative injury, a potential aspect of numerous disease processes.