Clinical implications of oxidative stress and antioxidant therapy.

Oxidative stress occurs when there is an imbalance between generation of reactive oxygen species and inadequate antioxidant defense systems. Oxidative stress can cause cell damage either directly or through altering signaling pathways. Oxidative stress is a unifying mechanism of injury in many types of disease processes, including gastrointestinal diseases. For example, in alcoholic liver disease, reactive oxygen species have been detected through direct spin-trapping techniques and through indirect markers, such as products of lipid peroxidation. A host of antioxidants have protected against liver injury in animal models of alcoholic liver disease. Similarly, in inflammatory bowel disease, oxidative stress has been postulated to play a role in disease initiation and progression, and antioxidant therapy, such as green tea polyphenols and gene therapy with superoxide dismutase, has a markedly attenuated disease. Downregulation of specific detoxification genes may play a role in the pathogenesis of inflammatory bowel disease, especially in ulcerative colitis. Oxidative stress is postulated to play a sustaining role in acute and chronic pancreatitis. Antioxidant supplementation has been used with some success in the treatment of chronic pancreatitis. This review covers recent findings related to oxidative stress in liver disease, inflammatory bowel disease, and pancreatitis.