Univ Rennes, INSERM, INRA, Institut NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France.
Pharmacy Unit, Pontchaillou University Hospital, Rennes, France.
Drug Metab Rev. 2019 Nov;51(4):545-561. doi: 10.1080/03602532.2019.1679169. Epub 2019 Oct 24.
This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol's harmful effects or accentuate its beneficial effects.
本文总结了近期关于乙醇及其代谢物(乙醛)的毒性和有益作用的实验和流行病学数据,并重点介绍了它们的免疫调节作用。讨论酒精毒性作用的部分不仅考虑了急性毒性,还重点关注了其慢性毒性(肝脏疾病、致癌作用、心血管疾病、神经精神障碍、成瘾和戒断综合征、血液疾病、生殖毒性、骨质疏松症)。文章还强调了乙醇氧化代谢通过醇脱氢酶、细胞色素 P450 2E1 和乙醛脱氢酶的作用,以及遗传多态性对其病理生理学的影响。讨论乙醇及其代谢物(特别是 NLRP3 炎性小体途径)的有益作用(对心血管系统、糖尿病、神经系统和感觉器官、自身免疫性疾病和风湿病)的部分,突出了这些观察结果中抗炎和免疫调节作用的重要性。通过关注乙醇及其代谢物的免疫调节作用,特别是 NLRP3 炎性小体途径,这方面的知识可能有助于开发能够减轻乙醇有害作用或增强其有益作用的治疗方法。