Romero F J, Bosch-Morell F, Romero M J, Jareño E J, Romero B, Marín N, Romá J
Department of Physiology, School of Medicine and Dentistry, University of Valencia, Spain.
Environ Health Perspect. 1998 Oct;106 Suppl 5(Suppl 5):1229-34. doi: 10.1289/ehp.98106s51229.
Lipid peroxidation (LPO) is a free radical-related process that in biologic systems may occur under enzymatic control, e.g., for the generation of lipid-derived inflammatory mediators, or nonenzymatically. This latter form is associated mostly with cellular damage as a result of oxidative stress, which also involves cellular antioxidants in this process. This article focuses on the relevance of two LPO products, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), to the pathophysiology of human disease. The former has been studied in human serum samples of hepatitis C virus-infected adults and human immunodeficiency virus-infected children. In these two cases it is shown that the specific assay of serum MDA is useful for the clinical management of these patients. The presence of MDA in subretinal fluid of patients with retinal detachment suggests the involvement of oxidative stress in this process. Moreover, we were able to report the dependence of this involvement on the degree of myopia in these patients. The assay of MDA contents in the peripheral nerves of rats fed a chronic alcohol-containing diet or diabetic mice also confirms the pathophysiologic role of oxidative stress in these experimental models. In these two cases, associated with an increase in tissue LPO products content, we detected a decrease of glutathione peroxidase (GSHPx) activity in peripheral nerve, among other modifications. We have demonstrated that in vitro HNE is able to inhibit GSHPx activity in an apparent competitive manner, and that glutathione may partially protect and/or prevent this inactivation. The accumulation of LPO products in the brain of patients with Alzheimer's disease has also been described, and it is on the basis of this observation that we have tried to elucidate the role of oxidative stress and cellular antioxidants in beta-amyloid-induced apoptotic cell death of rat embryo neurons. Finally, we discuss the possible role of the observed vascular effects of HNE on human arteries.
脂质过氧化（LPO）是一个与自由基相关的过程，在生物系统中，它可能在酶的控制下发生，例如用于生成脂质衍生的炎症介质，或者以非酶促方式发生。后一种形式主要与氧化应激导致的细胞损伤有关，在这个过程中细胞抗氧化剂也会参与其中。本文重点关注两种LPO产物，丙二醛（MDA）和4-羟基壬烯醛（HNE）与人类疾病病理生理学的相关性。前者已在丙型肝炎病毒感染的成年人和人类免疫缺陷病毒感染的儿童的血清样本中进行了研究。在这两种情况下，血清MDA的特异性检测对于这些患者的临床管理是有用的。视网膜脱离患者的视网膜下液中存在MDA表明氧化应激参与了这个过程。此外，我们能够报告这种参与与这些患者近视程度的相关性。对喂食含慢性酒精饮食的大鼠或糖尿病小鼠的外周神经中MDA含量的检测也证实了氧化应激在这些实验模型中的病理生理作用。在这两种情况下，随着组织LPO产物含量的增加，我们检测到外周神经中谷胱甘肽过氧化物酶（GSHPx）活性降低以及其他变化。我们已经证明，在体外，HNE能够以明显的竞争性方式抑制GSHPx活性，并且谷胱甘肽可能部分保护和/或防止这种失活。阿尔茨海默病患者大脑中LPO产物的积累也有描述，基于这一观察结果，我们试图阐明氧化应激和细胞抗氧化剂在β-淀粉样蛋白诱导的大鼠胚胎神经元凋亡细胞死亡中的作用。最后，我们讨论了观察到的HNE对人类动脉的血管效应的可能作用。
