THE EFFECT OF IRON OVERLOAD ON RAT PLASMA AND LIVER OXIDANT STATUS IN-VIVO

There is ample evidence implicating reactive oxygen species in a numbe r of human degenerative diseases such as atherosclerosis and haemochro matosis. Although lipid peroxidation underlies many of the toxic effec ts of oxidative stress, there is a lack of a sensitive and reliable me thod for its assessment in vivo. To understand the implications of oxi dative stress in vivo, we have used dietary iron overload (IO) in the rat. Oxidant status in these animals was determined by assessing deple tion of endogenous antioxidants and formation of various lipid peroxid ation products, including acylated F-2-isoprostanes, a novel class of free-radical-derived prostaglandin-F-2-like compounds. IO led to a sig nificant decrease in the concentrations of the antioxidants alpha-toco pherol and ascorbic acid in plasma, and alpha-tocopherol, beta-caroten e and ubiquinol-10 in liver. Whereas there was no significant lipid pe roxidation in plasma, hepatic F-2-isoprostane levels were moderately b ut significantly increased in IO. In addition, IO caused a significant increase in plasma total and high-density lipoprotein cholesterol lev els, an effect that was correlated with depletion of plasma ascorbic a cid but not alpha-tocopherol. The data demonstrate that IO causes lipi d metabolism disturbances and oxidative stress which is associated wit h substantial depletion of endogenous antioxidants and moderate lipid peroxidative damage.