Acetaldehyde Adducts in Alcoholic Liver Disease

Setshedi, Mashiko; Wands, Jack R; de la Monte, Suzanne M

Acetaldehyde Adducts in Alcoholic Liver Disease

Journal Article

2010

Journal Title

Oxidative Medicine and Cellular Longevity

Link to Journal

https://dx.doi.org/10.4161/oxim.3.3.12288

Department

Department of Medicine

Faculty

Faculty of Health Sciences

Abstract

Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD), with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC). Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15%) versus cirrhosis (15–20%) is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.