Niemelä O, Juvonen T, Parkkila S
Department of Clinical Chemistry, Oulu University Central Hospital, Finland.
J Clin Invest. 1991 Apr;87(4):1367-74. doi: 10.1172/JCI115141.
Acetaldehyde, the toxic product of ethanol metabolism in the liver, covalently binds to a variety of proteins. Recent studies indicate that such binding can stimulate the production of antibodies against the acetaldehyde adducts. We raised rabbit antibodies which recognized various protein-acetaldehyde conjugates but not the corresponding control proteins. Such antibodies were used in immunohistochemical studies to find out whether acetaldehyde-generated epitopes can be detected from liver specimens of 13 human subjects with different degrees of alcohol consumption. While the specimens obtained from alcohol abusers (n = 4) and alcoholics (n = 3) exhibited marked positive staining for acetaldehyde adducts inside the hepatocytes in a granular uneven pattern, the control samples (n = 6) were almost devoid of immunoreactivity. In the alcohol abusers with an early stage of alcohol-induced liver damage, staining was detected exclusively around the central veins. The data indicate that intracellular acetaldehyde adducts occur in the centrilobular region of the liver of individuals consuming excessive amounts of alcohol. Immunohistochemical detection of such adducts may prove to be of value in the early identification of alcohol abuse and in elucidating the mechanisms of alcohol-induced organ damage.
乙醛是肝脏中乙醇代谢产生的有毒产物,它能与多种蛋白质共价结合。最近的研究表明,这种结合可刺激针对乙醛加合物的抗体产生。我们制备了兔抗体,该抗体能识别各种蛋白质 - 乙醛缀合物,但不能识别相应的对照蛋白质。这些抗体被用于免疫组织化学研究,以确定是否能从13名不同酒精摄入量的人类受试者的肝脏标本中检测到乙醛产生的表位。从酗酒者(n = 4)和酒精性肝病患者(n = 3)获取的标本中,肝细胞内乙醛加合物呈现明显的阳性染色,呈颗粒状不均匀分布,而对照样本(n = 6)几乎没有免疫反应性。在处于酒精性肝损伤早期的酗酒者中,仅在中央静脉周围检测到染色。数据表明,细胞内乙醛加合物出现在过量饮酒者肝脏的小叶中央区域。此类加合物的免疫组织化学检测可能在酒精滥用的早期识别以及阐明酒精诱导器官损伤的机制方面具有价值。