RESEARCH UPDATE OXIDATIVE STRESS AND ALCOHOLIC LIVER DISEASE

Toxic substances generated during the metabolism of alcohol in the liver may contribute to the development of alcoholic liver disease. These substances include highly reactive molecules that can destroy vital cell components through a process called oxidation. Cells are protected against oxidation by the action of certain enzymes, vitamins, and other substances, known collec-tively as antioxidants. An imbalance between oxidants and antioxidants can lead to oxidative stress, character-ized by escalating cell damage. Evidence suggests that the major energy-generating structures within cells (i.e., mitochondria) may be especially sensitive to oxidative stress, resulting in diminished energy production. Medications that reduce oxidative stress in mitochon-dria may ameliorate liver disease. KEY WORDS: ethanol metabolism; physiological stress; oxidation-reduction; pathogenesis; alcoholic liver disorder; glutathione; mitochondria; inflammation; literature review The metabolism of toxic substances that enter the bodyoccurs largely in the liver. Among these toxic sub-stances is alcohol, which is eventually broken down into simple end products for easy elimination. However, certain byproducts generated during alcohol metabolism may be more toxic than alcohol itself and may contribute to the development of alcoholic liver disease (ALD) (Ashak et al. 1991). These byproducts include oxygen-containing molecules that can destroy vital cell components through a chemical process called oxidation. The first report implicating oxidative processes in the development of ALD was published in the early 1960’s by DiLuzio, who observed that alcohol administration promoted the oxidative breakdown of cell membranes (DiLuzio 1964; DiLuzio and Hartman 1967). DiLuzio further demonstrated that substances which inhibit oxida-tion (i.e., antioxidants) could prevent alcohol-induced membrane damage. From this early research arose the concept that an imbalance between oxidants and antioxi-dants can create oxidative stress, a state marked by con-tinued production of oxidizing agents and escalating cell damage. This article explores alcohol metabolism and oxidative stress, the balance between oxidants and antiox-idants, and the potential use of antioxidants to treat ALD