Iron-Induced Oxidant Stress Leads to Irreversible Mitochondrial Dysfunctions and Fibrosis in the Liver of Chronic Iron-Dosed Gerbils. The Effect of Silybin

Hepatic iron toxicity because of iron overload seems to be mediated by lipid peroxidation ofbiological membranes and the associated organelle dysfunctions. However, the basicmechanisms underlying this process in vivo are still little understood. Gerbils were dosed with weeklyinjections of iron—dextran alone or in combination with sylibin, a well—known antioxidant,by gavage for 8 weeks. A strict correlation was found between lipid peroxidation and the levelof desferrioxamine chelatable iron pool. A consequent derangement in the mitochondrialenergy-transducing capability, resulting from a reduction in the respiratory chain enzymeactivities, occurred. These irreversible oxidative anomalies brought about a dramatic drop intissue ATP level. The mitochondrial oxidative derangement was associated with thedevelopment of fibrosis in the hepatic tissue. Silybin administration significantly reduced bothfunctional anomalies and the fibrotic process by chelating desferrioxamine chelatable iron.