Godin D V, Dahlman D M
Department of Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada.
Res Commun Chem Pathol Pharmacol. 1993 Feb;79(2):151-66.
Uncontrolled oxidation has been implicated in the pathogenesis of atherosclerosis. In order to investigate the possible influence of hyperlipidemia on endogenous antioxidant status, the effects of dietary cholesterol supplementation on antioxidant enzymes and in vitro susceptibility to oxidative challenge (as measured by glutathione depletion and lipid peroxidation) were compared in two species exhibiting high and low susceptibilities to atherosclerosis, namely Japanese quail and rat, respectively. Standard diets were supplemented with cholesterol and cholic acid (1.0 and 0.5%, by weight, respectively) and assessments of antioxidant status made in red cells, liver, kidney and heart after 1, 2, 5 and 8 weeks. In contrast to the absence of detectable antioxidant alterations in rats, quail showed complex tissue-dependent changes, including increases (possibly adaptive) in antioxidant enzyme activities (usually first apparent at 2 weeks), enhanced susceptibility to peroxide-induced glutathione depletion (heart, kidney and liver) at 5 weeks and decreased sensitivity to lipid oxidation (heart and liver) at 8 weeks. Our results indicate an association of hyperlipidemia with complex time-dependent alterations in antioxidant components in an atherosclerosis-susceptible species prior to the appearance of visible atherosclerotic lesions. Future studies will focus on alterations in antioxidant components associated with atherosclerotic plaque development.
不受控制的氧化作用与动脉粥样硬化的发病机制有关。为了研究高脂血症对内源性抗氧化状态的可能影响，分别在对动脉粥样硬化敏感性高和低的两个物种（即日本鹌鹑和大鼠）中比较了膳食补充胆固醇对抗氧化酶以及体外氧化应激易感性（通过谷胱甘肽消耗和脂质过氧化测量）的影响。标准饮食分别补充胆固醇和胆酸（重量分别为1.0%和0.5%），并在1、2、5和8周后对红细胞、肝脏、肾脏和心脏的抗氧化状态进行评估。与大鼠未检测到抗氧化变化相反，鹌鹑表现出复杂的组织依赖性变化，包括抗氧化酶活性增加（可能是适应性的，通常在2周时首次明显），5周时对过氧化物诱导的谷胱甘肽消耗的易感性增强（心脏、肾脏和肝脏），以及8周时对脂质氧化的敏感性降低（心脏和肝脏）。我们的结果表明，在可见动脉粥样硬化病变出现之前，高脂血症与动脉粥样硬化易感物种中抗氧化成分复杂的时间依赖性变化有关。未来的研究将集中在与动脉粥样硬化斑块发展相关的抗氧化成分变化上。
