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Food Types, Dietary Supplements, and Roles
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
The balance between the various ADH and ALDH isoforms regulates the concentration of acetaldehyde, which is important as a key risk factor for the development of alcoholism (49–50). Acetaldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for metabolism of the alcohol metabolite acetaldehyde in the liver (49). Certain individuals, usually of Asian origin (China, Japan, Korea, Vietnam), have an inactive mitochondrial ALDH2 because of a genetic ALDH deficiency. Of note, approximately 8% of the world’s population, and approximately 30–40% of the population in East Asia, carry an inactive ALDH2 gene (49). Thus, when these individuals consume ethanol, blood levels of acetaldehyde are 5-to 20-fold higher than those found in individuals with the active ALDH allele. Individuals with the inactive ALDH show marked vasodilator (facial flushing or red face), nausea, headaches, and palpitation when consuming alcohol (50). Acetaldehyde is poorly eliminated by these individuals and as a consequence, little alcohol is consumed. ALDH2 deficient individuals are at lower risk for alcoholism. In contrast, they may have possibly increased risk for liver damage and esophageal cancer if alcohol continues to be consumed due to the accumulation of acetaldehyde in these organs (49–51).
Alcohol-Induced Hepatotoxicity
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
All known oxidative pathways of ethanol metabolism result in the production of acetaldehyde. Its metabolism and general effects have been reviewed elsewhere (Lieber, 1982, 1988d). Acetaldehyde is converted to acetate by acetaldehyde dehydrogenase, an enzyme with an interesting polymorphism and associated striking consequences in terms of ethanol intolerance and flushing, exhibited by subjects who harbor an inactive aldehyde dehydrogenase variant (Harada et al., 1980; Yoshida et al., 1984). These aspects will not be discussed in detail here; we shall focus instead on aspects of the toxicity of acetaldehyde most conspicuously related to liver injury.
Disposition and Metabolism of Drugs of Dependence
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
Using ethanol containing deuterium, it has been demonstrated that the hydrogen atom transferred to NAD comes directly from the α-carbon of ethanol.465 Acetaldehyde dehydrogenase catalyzes the oxidation of acetaldehyde to acetic acid.470,471
Taxifolin, a novel food, attenuates acute alcohol-induced liver injury in mice through regulating the NF-κB-mediated inflammation and PI3K/Akt signalling pathways
Published in Pharmaceutical Biology, 2021
Chuanbo Ding, Yingchun Zhao, Xueyan Chen, Yinan Zheng, Wencong Liu, Xinglong Liu
The liver is an important part of the body’s metabolic system, which can remove many harmful substances from the body, but it is also attacked and damaged by many harmful substances. When the body is stimulated by a large amount of alcohol, about 90% of the alcohol content is metabolized in the liver, which will cause severe hepatotoxicity. Alcohol dehydrogenase in the cytoplasm of liver cells will metabolize ethanol into acetaldehyde, aldehyde dehydrogenase (ALDH) or other isoenzymes. The lack of acetaldehyde dehydrogenase leads to the accumulation of acetaldehyde, and excess acetaldehyde produces a large amount of reactive oxygen species (ROS), which in turn leads to oxidative stress, hepatic stellate cells (HSCs) and cause severe hepatotoxicity (Cui et al. 2019). In addition, the hepatocytes were directly stimulated by the ethanol and acetaldehyde accumulated in the liver, which can cause degeneration and necrosis of liver cells, and aggravate hepatocyte apoptosis (Li et al. 2017). Furthermore, studies have shown that oxidative stress injury caused by excessive accumulation of acetaldehyde may promote the excessive release of macrophages and many proinflammatory factors, including TNF-α, IL-1β, nuclear factor-kappa B (NF-κB), nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) (Li et al. 2016). Therefore, inflammatory injury is a key pathological process leading to the development of alcoholic liver toxicity, which also provides many target references for the clinical treatment of alcoholic liver toxicity.
Pharmacotherapeutic management of co-morbid alcohol and opioid use
Published in Expert Opinion on Pharmacotherapy, 2020
Lauren E. Hood, Jonna M. Leyrer-Jackson, M. Foster Olive
Disulfiram is intended to provide aversive conditioning against alcohol to promote abstinence. Disulfiram causes increased sensitivity to the negative effects of alcohol by inhibiting acetaldehyde dehydrogenase 2 (ALDH2), an important enzyme for metabolizing acetaldehyde to acetate. Acetaldehyde is the first byproduct of alcohol oxidation, and when disulfiram is metabolized in the presence of alcohol, the lack of functional ALDH2 leads to the accumulation of acetaldehyde in the bloodstream. The increased concentration of acetaldehyde causes unpleasant symptoms characteristic of a severe hangover, including nausea, vomiting, headaches, and low blood pressure [2]. The severity of the reaction experienced is dependent on the dose of disulfiram and the amount of alcohol consumed, and has the potential to be fatal under some circumstances [81]. In the absence of alcohol, disulfiram induces minor side effects including drowsiness, headaches and an increased risk for heptatoxicity that is preventable if monitored properly [81]. In the same mechanistic vein, mutations in the Aldh2 gene that impede acetaldehyde metabolism appear to be protective against AUDs. For example, the ALDH2.2 allele, predominantly expressed in Asian populations, encodes a nonfunctional form of the enzyme and confers sensitivity to alcohol, most frequently characterized by facial flushing [83,84].
On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications
Published in Expert Review of Precision Medicine and Drug Development, 2020
Steven J. Nieto, Erica N. Grodin, Lara A. Ray
Several candidates and genome-wide association studies implicate alcohol metabolism genes in risk for AUD. Unfortunately, few studies have examined the influence of these genes on AUD medications. For the most part, alcohol metabolism occurs in the liver wherein several enzymes oxidize alcohol. Alcohol dehydrogenase converts alcohol to acetaldehyde, a potentially toxic metabolite, which is usually rapidly converted to acetic acid by the enzyme acetaldehyde dehydrogenase. Acetaldehyde dehydrogenase (ALDH) occurs in several genetic forms with differential activity. More than one third of individuals with East Asian ancestry inherit the inactive form of ALDH2 [79]. For these individuals, alcohol consumption increases levels of acetaldehyde, causing several negative physiological consequences, such as nausea and vomiting. Thus, inactive ALDH2 may enhance treatment response to drugs that block acetaldehyde metabolism, such as disulfiram. Yoshimura et al. [80] found that alcohol dependent individuals (ICD-9 criteria) with the inactive ALDH2 genotype had higher rates of abstinence from alcohol when treated with disulfiram relative to carriers treated with placebo. Prospective clinical studies with larger sample sizes are needed to examine the influence of alcohol metabolism genes.