Niemelä O, Parkkila S, Ylä-Herttuala S, Halsted C, Witztum J L, Lanca A, Israel Y
Department of Clinical Chemistry, Univeristy of Oulu, Finland.
Lab Invest. 1994 Apr;70(4):537-46.
The primary mechanisms of ethanol-induced tissue damage have been suggested to include aldehyde-derived protein modifications resulting from ethanol metabolism and lipid peroxidation. Conjugation of reactive aldehydes to a variety of target proteins and cellular constituents have been recently reported. This research was undertaken in order to examine the presence of covalent chemical addition products (adducts) of proteins and acetaldehyde, the first metabolite of ethanol, and those with malondialdehyde, a product of lipid peroxidation, as formed in vivo.
Specific antibodies recognizing acetaldehyde- and malondialdehyde-modified epitopes in proteins were used in immunoperoxidase and double immunofluorescence stainings of liver specimens obtained from ethanol-fed rats and micropigs and from human alcoholics.
The centrilobular region of the liver contained the protein modifications both in alcohol-consuming humans and in animals fed ethanol before any apparent histologic damage. With inflammation and fibrosis, such protein modifications were more widespread, and the positive staining for the malondialdehyde-derived modification became more dominant. The presence of the adducts colocalized with the areas of fatty infiltration, focal necrosis and fibrosis. In addition, the erythrocytes of alcohol consumers were found to contain such modifications.
The studies support the view that covalent damage to proteins and cellular constituents induced by aldehyde-derived modifications in vivo may play a role in the sequence of events leading to liver disease in alcohol consumers. Species and dietary differences may be important in the relative contribution of lipid peroxidation to alcohol-induced tissue damage.
乙醇诱导组织损伤的主要机制被认为包括乙醇代谢产生的醛衍生蛋白修饰以及脂质过氧化。最近有报道称活性醛与多种靶蛋白和细胞成分发生共轭反应。本研究旨在检测乙醇的第一种代谢产物乙醛以及脂质过氧化产物丙二醛与蛋白质在体内形成的共价化学加成产物（加合物）。
使用识别蛋白质中乙醛和丙二醛修饰表位的特异性抗体，对从喂食乙醇的大鼠、小型猪以及人类酗酒者获取的肝脏标本进行免疫过氧化物酶染色和双重免疫荧光染色。
在出现任何明显的组织学损伤之前，饮酒的人类和喂食乙醇的动物肝脏的小叶中央区域均存在蛋白质修饰。随着炎症和纤维化的出现，此类蛋白质修饰更为广泛，且丙二醛衍生修饰的阳性染色变得更加显著。加合物的存在与脂肪浸润、局灶性坏死和纤维化区域共定位。此外，发现饮酒者的红细胞含有此类修饰。
这些研究支持以下观点，即体内醛衍生修饰诱导的蛋白质和细胞成分的共价损伤可能在导致饮酒者肝病的一系列事件中起作用。物种和饮食差异在脂质过氧化对乙醇诱导的组织损伤的相对贡献中可能很重要。
