Liver injury and generation of hydroxyl free radicals in experimental secondary hemochromatosis.
An experimental model of secondary hemochromatosis is described. Saccharated iron was administered i.v. to rats for 7 months in total doses in the range 1.0-1.7 g per kg body weight. After the completion of iron loading, the biochemical measurements revealed elevation of alanine aminotransferase (ALT), slight reduction of plasma glucose concentration, and significant reduction of both plasma and liver ascorbic-acid levels. The mean liver iron concentration was 50 times higher in iron-loaded animals than in controls. High concentrations of inorganic iron were also observed in spleen, pancreas, and heart. Histologic analysis revealed marked hepatic fibrosis in most animals in the experimental group. These results demonstrate this animal model presents some pathologic findings observed in human transfusional hemochromatosis. Additionally, hydroxyl free radicals were detected by electron paramagnetic resonance (EPR) spectroscopy in the iron-overloaded liver tissue processed at pH 5.0. No free radicals were detected at pH 7.4. These results suggest the possible participation of hydroxyl free radicals in the cellular toxicity of iron overload.
Department of Clinical Medicine, School of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
M S
MS
Figueiredo
O
O
Baffa
J
J
Barbieri Neto
M A
MA
Zago
D000818:Animals; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D005355:Fibrosis; D005609:Free Radicals; D006432:Hemochromatosis / Q000139:chemically induced / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000378:metabolism; D007501:Iron; D008099:Liver / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000473:pathology
D005609:Free Radicals; D006878:Hydroxides; D007501:Iron