Role of iron in alcoholic liver disease: introduction and summary of the symposium

Vishnudutt Purohit, Denise Russo, Marvin Salin
Alcohol 2003, 30 (2): 93-7
12957291
The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on the "Role of Iron in Alcoholic Liver Disease" at Bethesda, Maryland, USA, October 2002. Alcoholic liver disease is a major cause of illness and death in the United States. Oxidative stress plays a key role in the pathogenesis of alcoholic liver disease. Iron can induce oxidative stress by catalyzing the conversion of superoxide and hydrogen peroxide to more potent oxidants such as hydroxyl radicals, which can cause tissue injury by initiating lipid peroxidation and causing oxidation of proteins and nucleic acids. Increasing evidence supports the suggestion that iron plays a significant role in the pathogenesis of alcoholic liver disease by exacerbating oxidative stress. Understanding the underlying mechanisms by which iron participates in the initiation and development of alcoholic liver disease may help design strategies for the treatment and prevention of the disease. For this symposium, nine speakers were invited to address the following issues: (1) iron intake from foods and dietary supplements; (2) hepatic iron overload in alcoholic liver disease; (3) iron-dependent activation of nuclear factor-kappa B (NF-kappaB) in Kupffer cells; (4) iron and cytochrome P450 2E1 (CYP2E1)-dependent oxidative stress and liver toxicity; (5) iron-induced oxidative stress in alcoholic hepatic fibrogenesis; (6) hemochromatosis and alcoholic liver disease; (7) iron as a co-morbid factor in nonhemochromatotic liver diseases; (8) iron and liver cancer; and (9) iron chelators and iron toxicity. On the basis of these presentations, it is concluded that heavy alcohol intake can result in increased accumulation of iron in the liver, in both hepatocytes and Kupffer cells. Iron-induced oxidative stress may promote the severity of alcoholic liver disease by (1) inducing NF-kappaB activation and subsequently increasing transcription of proinflammatory cytokines in Kupffer cells; (2) exacerbating CYP2E1-induced oxidative stress, especially in hepatocytes, through production of more toxic hydroxyl radicals; (3) stimulating hepatic stellate cells to produce excess amount of collagen and other matrix proteins that can lead to fibrosis; and (4) causing DNA damage and mutations that promote the development of liver cancer. Dietary iron supplements may further exacerbate the severity of alcoholic liver disease by increasing the magnitude of oxidative stress. We hope that the studies presented will stimulate further research in this exciting area.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
12957291
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"