Iron overload and kidney lysosomes.
Iron overload has been associated with damage of the liver and other organs of patients with primary or secondary increased iron load. In order to study the effect of iron overload on the pathophysiology of kidney lysosomes, experimentally induced iron overload models were employed. Iron overload was achieved through intraperitoneal injections of Fe-dextran (Imferon) in male rats, at different final iron concentrations (825 and 1650 mg/kg, single and double dose groups respectively). Controls were injected with dextran following a similar protocol. The animals were killed at different time points after the last injection. Subcellular fractionation studies of kidney homogenates were carried out by differential centrifugation and density gradient centrifugation. The kidney iron load was increased with both doses. Iron appeared to accumulate mainly in the lysosomes, bringing about distinct changes in the behaviour of the organelles as judged by subcellular fractionation studies. Lysosomes became more fragile and showed increased density. The extent of the above changes seemed to correlate with the extent and duration of iron accumulation and could be reversed when the iron load was reduced.
Dimitriou
E
E
Institute of Child Health, 'Aghia Sophia' Children's Hospital, Athens, Greece. inchildh@otenet.gr
Kairis
M
M
Sarafidou
J
J
Michelakakis
H
H
D000818:Animals; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D006485:Hemosiderin / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000503:physiopathology*; D007505:Iron-Dextran Complex / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008361:Mannosidases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D043323:alpha-Mannosidase; D001616:beta-Galactosidase / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D007505:Iron-Dextran Complex; D006485:Hemosiderin; D007501:Iron; D008361:Mannosidases; D001616:beta-Galactosidase; D043323:alpha-Mannosidase; D001619:beta-N-Acetylhexosaminidases