Merck

Alcohol induced hepatic fibrosis: role of acetaldehyde.

Molecular aspects of medicine (2008-01-01)
Tommaso Mello, Elisabetta Ceni, Calogero Surrenti, Andrea Galli
ABSTRACT

Alcohol abuse is one of the major causes of liver fibrosis worldwide. Although the pathogenesis of liver fibrosis is a very complex phenomenon involving different molecular and biological mechanisms, several lines of evidence established that the first ethanol metabolite, acetaldehyde, plays a key role in the onset and maintenance of the fibrogenetic process. This review briefly summarizes the molecular mechanisms underlying acetaldehyde pro-fibrogenic effects. Liver fibrosis represents a general wound-healing response to a variety of insults. Although mortality due to alcohol abuse has been constantly decreasing in the past 20 years in Southern Europe and North America, in several Eastern-European countries and Great Britain Alcoholic Liver Disease (ALD) shows a sharply increasing trend [Bosetti, C., Levi, F., Lucchini, F., Zatonski, W.A., Negri, E., La, V.C., 2007. Worldwide mortality from cirrhosis: an update to 2002. J. Hepatol. 46, 827-839]. ALD has a complex pathogenesis, in which acetaldehyde (AcCHO), the major ethanol metabolite, plays a central role. Ethanol is mainly metabolized in the liver by two oxidative pathways. In the first one ethanol is oxidized to acetaldehyde by the cytoplasmic alcohol dehydrogenase enzyme (ADH), acetaldehyde is then oxidized to acetic acid by the mitochondrial acetaldehyde dehydrogenase (ALDH). The second pathway is inducible and involves the microsomal ethanol-oxidizing system (MEOS), in which the oxidation of ethanol to acetaldehyde and acetic acid also leads to generation of reactive oxygen species (ROS). Chronic ethanol consumption significantly inhibits mitochondrial ALDH activity while the rate of ethanol oxidation to acetaldehyde is even enhanced, resulting in a striking increase of tissue and plasma acetaldehyde levels [Lieber, C.S., 1997. Ethanol metabolism, cirrhosis and alcoholism. Clin. Chim. Acta 257, 59-84]. This review will focus on the molecular mechanisms by which acetaldehyde promote liver fibrosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetaldehyde solution, 50 wt. % in ethanol
Sigma-Aldrich
Acetaldehyde solution, natural, 50 wt. % ethanol, FG
Sigma-Aldrich
Acetaldehyde solution, 40 wt. % in isopropanol
Sigma-Aldrich
Acetaldehyde solution, 40 wt. % in H2O
Sigma-Aldrich
Acetaldehyde solution, 5 M in THF
Sigma-Aldrich
Acetaldehyde, natural, FG
Sigma-Aldrich
Acetaldehyde, ACS reagent, ≥99.5%
Supelco
Acetaldehyde, puriss. p.a., anhydrous, ≥99.5% (GC)
Supelco
Acetaldehyde, ReagentPlus®, ≥99.0% (GC)
Supelco
Acetaldehyde, PESTANAL®, analytical standard