Lipid Peroxidation and Bioactivation of Halogenated Hydrocarbons in Rat Liver Mitochondria During Experimental Siderosis
It is firmly extablished that increased amount of iron accumulated in hepatic parenchymal cells is associated with tissue injury, fibrosis and ultimately, cirrhosis1. However, the pathogenetic mechanism of iron in determining the liver injury has not been experimentally proven2. Currently two hypothesis have been put forward in order to explain the hepatocellular injury in chronic iron overload. The first implies that the excess iron largely occurring in lysosomes, physically disrupts these organelles with the release of cell damaging hydrolytic enzymes3. The second one presupposes that the pathological accumulation of iron elicits membrane lipid peroxidation in cellular organelles resulting in structural and functional alterations of cell integrity4. Indeed, iron could promote the production of reactive oxygen species such as Superoxide anion (O·− 2), hydroxy radicals (OH·− 4), and hydrogen peroxide (H2O2)5. The experimental evidence, gathered up to now, indicates that chronic iron overload may induce in vivo lipid peroxidation of mitochcndrial membranes6–8. Furthermore, the in vivo occurrence of lipid peroxidation in the mitochondrial membranes has been suggested to be responsible for some anomalies in liver mitochondria isolated from rats made siderotic either by dietary iron9,10 or by intraperitoneal injection of iron-(III)- gluconate complex11–13.
KeywordsElectron Spin Resonance Iron Overload Liver Mitochondrion Carbonyl Iron Hepatic Iron Overload
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