THE PATHOPHYSIOLOGICAL SIGNIFICANCE OF LIPID-PEROXIDATION IN OXIDATIVE CELL INJURY
THE PATHOPHYSIOLOGICAL SIGNIFICANCE OF LIPID-PEROXIDATION IN OXIDATIVE CELL INJURY
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DOI：
10.1002/hep.1840070227
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发表时间：
1987-03-01
期刊：
影响因子：
13.5
通讯作者：
JONES, DP
中科院分区：
文献类型：
--
作者：
TRIBBLE, DL;TAK, YA;JONES, DP
虽然伴随氧化应激的复杂过程导致许多细胞组分的损伤，但膜脂质的过氧化分解和与之相关的大量膜性质的变化经常被认为是细胞损伤的基础。这一想法是在四氯化碳（CCL）和乙醇相关肝毒性的早期研究中提出的（1，2），并且一直存在，因为脂质过氧化提供了自由基引发的过程和相关细胞膜功能障碍之间的逻辑联系，并且因为脂质过氧化发生在许多不同肝毒素引起的细胞损伤的进展中。然而，虽然脂质过氧化的化学是众所周知的关于自由基形成的潜在机制（3，4），参与最终产物形成的反应序列（5，6）和细胞防御这种损伤（3，7，81），争议仍然是脂质过氧化在氧化性细胞损伤和死亡（5，6，9，10）的意义。这一争议的大部分可以归因于方法上的困难，在定义氧化损伤的关键不可逆步骤，并在准确定量的物种和完整组织中涉及的反应率。虽然存在大量证据表明，脂质过氧化作用在氧化应激细胞（lo）中增加，但尚不清楚细胞特性的相关变化是否是引起细胞损伤所必需的或足够大的。细胞死亡后发生的脂质过氧化不容易与可能与细胞损伤有因果关系的脂质过氧化区分开来。此外，引发脂质过氧化的自由基过程也会对其他大分子造成直接损伤，包括对蛋白质、核酸和碳水化合物的损伤，这些过程在细胞损伤中可能比脂质过氧化更重要（11）。在这篇综述中，我们考虑了一些方法上的困难，限制了识别毒性细胞损伤中脂质过氧化作用的因果作用的能力。考虑到这些，我们认为，脂质过氧化可能是更重要的自由基诱导的损伤的程度比直接造成的伤害调制。这种可能性是讨论各种毒素被认为是导致肝细胞损伤的氧化机制。
Although the complex processes which accompany oxidative stress result in damage to many cell components, peroxidative decomposition of membrane lipids and the associated changes in bulk membrane properties have frequently been considered as the basis of cell injury. This idea was put forth in early studies of carbon tetrachloride (CCL)-and ethanol-associated hepatotoxicity (1, 2) and has persisted because lipid peroxidation provides a logical link between free radical-initiated processes and associated cellular membrane dysfunction and because lipid peroxidation occurs in the progression of cellular injury from many diverse hepatotoxins. Yet, while the chemistry of lipid peroxidation is well known with regard to the potential mechanisms for radical formation (3, 4), the sequences of reactions involved in the formation of endproducts (5, 6) and the cellular defenses against such injury (3, 7, 81, controversy remains as to the significance of lipid peroxidation in oxidative cell injury and death (5, 6, 9, 10). Much of this controversy can be attributed to methodological difficulties in defining the critical irreversible steps in oxidative injury and in accurately quantitating the species and rates of reactions involved in intact tissues. While considerable evidence exists to show that lipid peroxidation increases in the oxidatively stressed cell (lo), it is not known whether the associated changes in cellular properties are necessary for or of a sufficient magnitude to cause cell injury. Lipid peroxidation which occurs after cell death is not easily distinguished from that which may be causally related to cell injury. Moreover, the radical processes which initiate lipid peroxidation also cause direct damage to other macromolecules, including damage to proteins, nucleic acids and carbohydrates, and these processes may be more important in cell injury than the peroxidation of lipids (11). In this review, we consider some of the methodological difficulties which limit the ability to discern a causal role for lipid peroxidation in toxic cell injury. With these in mind, we suggest that lipid peroxidation may be more important in modulating the extent of free radical-induced injury than in directly causing injury. This possibility is discussed in terms of a variety of toxins which are thought to cause hepatocellular injury by oxidative mechanisms.