Toxicity Of Acetaldehyde

Acetaldehyde causes injury through the formation of adducts with proteins, resulting in antibody formation, inactivation of many key enzymes, decreased deoxyribonucleic acid (DNA) repair, and alterations in cell structures such as microtubules, mitochondria, and plasma membranes (Lieber, 1988, 1992a). Acetaldehyde also promotes synthesis of hepatic collagen—the key protein of scar tissue; furthermore, it causes glutathione depletion, thereby exacerbating the toxicity mediated by free radicals, which results in lipid peroxidation and other tissue damage (Lieber, 1991b). Because of the far-reaching toxicity of this metabolite of etha-nol, some of the liver cells die; this attracts inflammatory cells, which results in the more severe stage of alcoholic hepatitis, one of the precursors to the ultimate scarring or cirrhosis.

Once there is cirrhosis, a number of complications ensue, including obstruction of blood flow— with portal hypertension (elevated pressure in the veins leading from the intestine to the liver) and internal, life-threatening bleeding of distended veins, so-called varices. There is also a buildup of water in the abdominal cavity, so-called ascites (Lieber, 1992a).

Acetaldehyde is particularly elevated if drinking occurs in pregnancy; it crosses the placenta (Karl et al., 1988) and has been incriminated in the pathogenesis of the Fetal Alcohol Syndrome (FAS), the most common preventable cause of cogenital abnormalities.

The bulk of acetaldehyde is oxidized to acetate by an acetaldehyde dehydrogenase of the liver mitochondria. Lack of the active form of the enzyme in some Asians explains their high blood acetalde-hyde and flushing reaction after alcohol. Dl-SULFIRAM (Antabuse—a drug used in recovering alcoholics) is an inhibitor of acetaldehyde dehydrogenase. It raises the acetaldehyde levels after drinking and thereby causes flushing and several adverse effects that can be utilized to sustain abstinence in patients motivated to take the compound.

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