Hepatic lipid peroxidation in vivo in rats with chronic iron overload.

A C T Peroxidative decomposition of cellular membrane lipids is a postulated mechanism of hepa- tocellular injury in parenchymal iron overload. In the present study, we looked for direct evidence of lipid peroxidation in vivo (as measured by lipid-conjugated diene formation in hepatic organelle membranes) from rats with experimental chronic iron overload. Both parenteral ferric nitrilotriacetate (FeNTA) administration and dietary supplementation with carbonyl iron were used to produce chronic iron overload. Bio- chemical and histologic evaluation of liver tissue con- firmed moderate increases in hepatic storage iron. FeNTA administration produced excessive iron de- position throughout the hepatic lobule in both hepa- tocytes and Kupffer cells, whereas dietary carbonyl iron supplementation produced greater hepatic iron overload in a periportal distribution with iron depo- sition predominantly in hepatocytes. Evidence for mitochondrial lipid peroxidation in vivo was demon- strated at all three mean hepatic iron concentrations studied (1,197,3,231, and 4,216 ,g Fe/g) in both mod- els of experimental chronic iron overload. In contrast, increased conjugated diene formation was detected in microsomal lipids only at the higher liver iron con- centration (4,161 ug Fe/g) achieved by dietary car- bonyl iron supplementation. When iron as either FeNTA or ferritin was added in vitro to normal liver homogenates before lipid extraction, no conjugated diene formation was observed. We conclude that the presence of conjugated dienes in the subcellular frac-