Chronic liver iron overload in the baboon by ferric nitrilotriacetate. Morphologic and functional changes with special reference to collagen synthesis enzymes.
Two baboons receiving intramuscular injections of ferric nitrilotriacetate over a two-year period were compared with two control baboons. The results indicate that in iron-overloaded animals: liver iron excess was major (maximal liver iron concentration values of 42 mumol/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); iron deposition, although less abundant than in sinusoidal cells, was pronounced within parenchymal cells; serum transaminase activities were markedly increased; rare foci of perisinusoidal fibrosis were observed in areas of massive iron overload; and 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: exerts a marked biochemical cytolytic effect; and does not produce significant hepatic fibrosis, possibly related to an inhibiting effect of ferric nitrilotriacetate complex on 4-prolyl-hydroxylase activity.
D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000009:adverse effects*; D006432:Hemochromatosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives*; D010215:Papio
D005290:Ferric Compounds; D003094:Collagen; D007501:Iron; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate