Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects

Abstract

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.

Non-oxidative ethanol metabolism in human hepatic cells in vitro: Involvement of uridine diphospho-glucuronosyltransferase 1A9 in ethylglucuronide production

“…Ethanol is the most consumed legal drug worldwide and is considered to be the third leading cause of death in the United States (Nutt et al, 2007). Chronic excessive consumption of ethanol is associated with multi-organ toxicities, including hepatic, neurologic, cardiovascular or hematologic disorders (Bühler and Mann 2011;Smith et al 2015;Osna et al 2017;Obad et al 2018;Le Daré et al 2019). Alcohol is also involved in carcinogenesis of mouth, esophageal, hepatic, colic and breast cancer (Seitz and Stickel 2007).…”

Alcohol Hangover Differentially Modulates the Processing of Relevant and Irrelevant Information

“…Of note, there are several mechanisms which could drive such differences, including differential modulation of gamma-aminobutyric acid (GABAergic) signaling by ethanol and its metabolite acetaldehyde, which is likely responsible for feeling hungover [23][24][25], and immunological parameters, including those related to inflammation While previous studies have suggested that acute alcohol intoxication does not seem to strongly impair S-R binding [22], this has never been investigated in the hungover state, which may functionally differ from the intoxicated state [17,18]. Of note, there are several mechanisms which could drive such differences, including differential modulation of gamma-aminobutyric acid (GABAergic) signaling by ethanol and its metabolite acetaldehyde, which is likely responsible for feeling hungover [23][24][25], and immunological parameters, including those related to inflammation [26,27]. To the best of our knowledge, it has furthermore never been investigated whether potential alcohol effects on this phenomenon could be different for the S-R binding of response-relevant target information vs. that of response-irrelevant distractor information.…”

Alcohol-Induced Neuropathy in Chronic Alcoholism: Causes, Pathophysiology, Diagnosis, and Treatment Options

“…Chronic alcohol consumption leads to malnutrition with dysfunctions in protein and lipid metabolism which affect the metabolic pathways and progression of ALN symptoms within the central and peripheral nervous systems [89]. The direct toxic effects of alcohol and its metabolites (mainly acetaldehyde) are crucial in ALN etiology [64].…”