Chronic liver iron overload in the baboon by ferric nitrilotriacetate

Abstract

Two baboons receiving intramuscular injections of ferric nitrilotriacetate over a two-year period were compared with two control baboons. The results indicate that in ironoverloaded animals: (1) liver iron excess was major (maximal liver iron concentration values of 42 μmol/100 mg dry weight for both animals vs 1.3±0.2 (mean±sd) in controls) and chronic (for 15 months liver iron concentrations were higher than 15); (2) iron deposition, although less abundant than in sinusoidal cells, was pronounced within parenchymal cells; (3) serum transaminase activities were markedly increased; (4) rare foci of perisinusoidal fibrosis were observed in areas of massive iron overload; and (5) a dramatic decrease in hepatic 4-prolyl-hydroxylase activity was found, in contrast with unchanged glucosyltransferase and galactosyltransferase activities. In conclusion these findings suggest that, in our model, chronic liver iron overload: (1) exerts a marked biochemical cytolytic effect; and (2) does not produce significant hepatic fibrosis, possibly related to an inhibiting effect of ferric nitrilotriacetate complex on 4-prolyl-hydroxylase activity.