VITAMIN-E DECREASES HEPATIC LEVELS OF ALDEHYDE-DERIVED PEROXIDATION PRODUCTS IN RATS WITH IRON OVERLOAD

Hepatic iron overload can cause lipid peroxidation with the formation of aldehydic products, hepatocellular injury, and fibrosis. Vitamin E (alpha-tocopherol) may prevent peroxidation-induced hepatic damage. We used confocal laser scanning microscopy, digital image analysis, and immunohistochemical methods to quantitate aldehyde-derived peroxidatio n products in the liver of rats with experimental iron overload with o r without supplemental vitamin E. A strong autofluorescent reaction co localizing with iron deposits was present in the livers of iron-loaded rats. Fluorescent granules were unevenly distributed in the cytosol o f both hepatocytes and Kupffer cells in the periportal regions. Immuno histochemical studies revealed the presence of malondialdehyde adducts in the periportal regions of the iron-loaded rats. Vitamin E suppleme ntation markedly reduced the fluorescence intensity and the amount of aldehyde-derived peroxidation products and changed the distribution of stainable iron and iron-associated peroxidation products such that th eir levels were much decreased in Kupffer cells. These results indicat e that aldehyde-derived covalent chemical addition products are formed in the liver in iron overload. Vitamin E supplementation markedly red uces the amount of these compounds and changes their cellular distribu tion. These findings should be implicated in the role of antioxidant t herapy in conditions causing iron overload and lipid peroxidation.