Niemelä O
Department of Clinical Chemistry, University of Oulu, Finland.
Scand J Clin Lab Invest Suppl. 1993;213:45-54. doi: 10.3109/00365519309090673.
Alcohol abuse and alcoholism continue to be a major threat to human health. Given their increasing incidence and the detrimental impact on society, it is actually surprising that no objective, specific indicators for the early detection of alcohol-related health problems are available. A diagnostic test for a disease involving excessive alcohol consumption should be extremely specific in order to achieve positive predictive power, and: ideally it should also be very sensitive in order to identify problem drinkers in broad screening programs. The present research indicates that such a test for alcohol abuse may be provided by measurements of covalent chemical addition products (adducts) of acetaldehyde with biologically stable macromolecules. It was recently demonstrated that proteins modified with acetaldehyde are formed in vivo and can induce an antibody response as a result of alcohol consumption. Monoclonal and polyclonal antibodies raised by immunizations against acetaldehyde-modified proteins recognize acetaldehyde adducts irrespective of the nature of the carrier protein. Use of such antibodies in sensitive two-site immunoenzymatic or immunofluorometric assays has indicated that high acetaldehyde adduct concentrations exist in the erythrocytes of alcohol abusers, in healthy volunteers after a bout of drinking, and also in alcohol consuming mothers who subsequently give birth to children with foetal alcohol effects. We have developed the first immunohistochemical techniques for the detection of acetaldehyde adducts in human tissues. The centrilobular region of the liver of alcohol abusers with an early stage of histological tissue damage was found to contain acetaldehyde-modified epitopes, whereas the adducts were more widespread in advanced liver disease. The diagnostic superiority of acetaldehyde adducts as markers of ethanol consumption is due to the fact that they represent true metabolites of ethanol and allow estimations of past alcohol consumption after the ethanol has been eliminated from the body. Investigations into the formation of acetaldehyde adducts in alcohol consumers do not only have diagnostic applications but also help to explain the pathogenesis of alcohol-induced organ damage. Many types of hypersensitivity and immune responses are brought about by acetaldehyde-modified proteins. In addition, such metabolites of ethanol also aggravate liver disease through disturbed protein function and stimulation of fibrogenesis.
酒精滥用和酒精中毒仍然是对人类健康的重大威胁。鉴于其发病率不断上升以及对社会的有害影响，实际上令人惊讶的是，目前尚无用于早期检测酒精相关健康问题的客观、具体指标。针对涉及过量饮酒的疾病的诊断测试应具有极高的特异性，以实现阳性预测能力，并且：理想情况下，它还应具有很高的敏感性，以便在广泛的筛查项目中识别出问题饮酒者。目前的研究表明，通过测量乙醛与生物稳定大分子的共价化学加成产物（加合物），可能提供一种针对酒精滥用的测试方法。最近有研究表明，乙醛修饰的蛋白质在体内形成，并且由于饮酒可诱导抗体反应。通过针对乙醛修饰蛋白进行免疫接种产生的单克隆抗体和多克隆抗体能够识别乙醛加合物而不受载体蛋白性质影响。在灵敏的双位点免疫酶测定法或免疫荧光测定法中使用此类抗体表明，酒精滥用者的红细胞中、健康志愿者饮酒后以及随后生下患有胎儿酒精影响的孩子的饮酒母亲体内，均存在高浓度的乙醛加合物。我们已经开发出了第一种用于检测人体组织中乙醛加合物的免疫组织化学技术。在组织学组织损伤早期阶段的酒精滥用者肝脏的小叶中央区域发现含有乙醛修饰的表位，而在晚期肝病中加合物分布更为广泛。乙醛加合物作为乙醇消费标志物的诊断优势在于，它们代表乙醇的真实代谢产物，并且在乙醇从体内消除后能够估算过去的饮酒量。对酒精消费者体内乙醛加合物形成的研究不仅具有诊断应用价值，而且有助于解释酒精性器官损伤的发病机制。许多类型的超敏反应和免疫反应是由乙醛修饰的蛋白质引起的。此外，乙醇的此类代谢产物还通过干扰蛋白质功能和刺激纤维生成加重肝脏疾病。
