Effects of colloidal iron overload on renal and hepatic siderosis and the femur in male rats.
Genetic hemochromatosis is an iron overload disorder, and osteopenic and osteoporotic. Femoral neck bone mineral density (BMD) appears to fall with rising hepatic iron concentrations. A critical role for iron in mediating tissue injury is played via hydroxyl radical formation in nephrotoxicity. We investigated the effects of a colloidal iron overload on renal function, organ siderosis, and femoral bone in male rats. Iron overload reduced body growth, and increased the weights of the liver and spleen. Marked deposition of iron was noted in liver and kidney. Activities of lactate dehydrogenase and alkaline phosphatase were decreased, and the concentrations of blood urea nitrogen and creatinine were increased with the reduction in plasma calcium and inorganic phosphorus levels, i.e. functions of the liver and kidney might be affected by reactive oxygen species such as the superoxide radical, H2O2, and the hydroxyl radical produced by overloaded iron. Damage to the proximal tubular epithelial cells of the kidney and a loss of connectivity of cancellous bone in the epiphysis and of trabecular bone in the metaphysis of the distal femur were observed in iron-overloaded rats with a reduction of femoral bone mineral density, i.e. reabsorption of calcium from the proximal tubular epithelial cells of the kidney might be affected and urinary discharge of calcium might be elevated. It was suggested that iron overload gave rise to osteoporosis combined with renal dysfunction and liver iron overload syndrome.
Kudo
H
H
Department of Clinical Medicine, Bunkyo Gakuin University, Tokyo, Japan.
Suzuki
S
S
Watanabe
A
A
Kikuchi
H
H
Sassa
S
S
Sakamoto
S
S
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood; D003102:Colloids / Q000737:chemistry; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005269:Femur / Q000503:physiopathology*; D006397:Hematinics / Q000378:metabolism / Q000633:toxicity; D007275:Injections, Intravenous; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000503:physiopathology*; D007505:Iron-Dextran Complex / Q000378:metabolism / Q000633:toxicity; D007674:Kidney Diseases / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008107:Liver Diseases / Q000503:physiopathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010024:Osteoporosis / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012806:Siderosis / Q000503:physiopathology*
D015415:Biomarkers; D003102:Colloids; D006397:Hematinics; D007505:Iron-Dextran Complex; D003404:Creatinine; D007501:Iron; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D002118:Calcium