Rintala J, Jaatinen P, Parkkila S, Sarviharju M, Kiianmaa K, Hervonen A, Niemelä O
School of Public Health, University of Tampere, International Graduate School in Neuroscience, Medical School, University of Tampere, Tampere Finland.
Alcohol Alcohol. 2000 Sep-Oct;35(5):458-63. doi: 10.1093/alcalc/35.5.458.
Acetaldehyde, the first metabolite of ethanol, has been shown to be capable of binding covalently to liver proteins in vivo, which may be responsible for a variety of toxic effects of ethanol. Acetaldehyde-protein adducts have previously been detected in the liver of patients and experimental animals with alcoholic liver disease. Although a role for acetaldehyde as a possible mediator of ethanol-induced neurotoxicity has also been previously suggested, the formation of protein-acetaldehyde adducts in brain has not been examined. This study was designed to examine the occurrence of acetaldehyde-protein adducts in rat brain after lifelong ethanol exposure. A total of 27 male rats from the alcohol-preferring (AA) and alcohol-avoiding (ANA) lines were used. Four ANA rats and five AA rats were fed 10-12% (v/v) ethanol for 21 months. Both young (n = 10) and old (n = 8) rats receiving water were used as controls. Samples from frontal cortex, cerebellum and liver were processed for immunohistochemical detection of acetaldehyde adducts. In four (two ANA, two AA rats) of the nine ethanol-exposed rats, weak or moderate positive reactions for acetaldehyde adducts could be detected both in the frontal cortex and cerebellum, whereas no such immunostaining was found in the remaining five ethanol-treated rats or in the control rats. The positive reaction was localized to the white matter and some large neurons in layers 4 and 5 of the frontal cortex, and to the molecular layer of the cerebellum. Interestingly, the strongest positive reactions were found among the ANA rats, which are known to display high acetaldehyde levels during ethanol oxidation. We suggest that acetaldehyde may be involved in ethanol-induced neurotoxicity in vivo through formation of adducts with brain proteins and macromolecules.
乙醛是乙醇的首个代谢产物，已被证明在体内能够与肝脏蛋白质共价结合，这可能是乙醇产生多种毒性作用的原因。先前在患有酒精性肝病的患者和实验动物的肝脏中已检测到乙醛 - 蛋白质加合物。尽管先前也有人提出乙醛可能是乙醇诱导神经毒性的一种介质，但尚未研究脑内蛋白质 - 乙醛加合物的形成情况。本研究旨在检测终生暴露于乙醇的大鼠脑内乙醛 - 蛋白质加合物的发生情况。总共使用了27只来自嗜酒（AA）和厌酒（ANA）品系的雄性大鼠。4只ANA大鼠和5只AA大鼠喂食10 - 12%（v/v）乙醇，持续21个月。接受水的年轻（n = 10）和年老（n = 8）大鼠用作对照。对额叶皮质、小脑和肝脏的样本进行处理，用于免疫组织化学检测乙醛加合物。在9只乙醇暴露大鼠中的4只（2只ANA大鼠和2只AA大鼠），在额叶皮质和小脑中均可检测到乙醛加合物的弱阳性或中度阳性反应，而在其余5只乙醇处理大鼠或对照大鼠中未发现此类免疫染色。阳性反应定位于额叶皮质第4层和第5层的白质和一些大神经元，以及小脑的分子层。有趣的是，在ANA大鼠中发现了最强的阳性反应，已知这些大鼠在乙醇氧化过程中乙醛水平较高。我们认为乙醛可能通过与脑蛋白质和大分子形成加合物而在体内参与乙醇诱导的神经毒性作用。
