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Toxicologic Pathology
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Articles

Experimental Renal Failure and Iron Overload: A Histomorphometric Study in Rat Tibia

Patricia M. Mandalunis and Angela M. Ubios

Department of Histology, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina

Correspondence: Address correspondence to: Patricia Mandalunis, Department of Histology, School of Dentistry, University of Buenos Aires, M.T. de Alvear 2142–1er. A, 1122 Buenos Aires, Argentina; e-mail:patricia{at}histo.odon.uba.ar

Renal failure (RF) is a serious disease of relatively high incidence, known to cause bone alterations. RF patients frequently suffer anemia, which is usually treated with iron. Given that iron overload inhibits bone formation, the aim of the present study was to evaluate the effect of iron on the subchondral bone of rat tibiae, using a model of renal failure. Male Wistar rats were subjected to experimental nephrectomy in order to induce renal failure and to iron overload by daily intraperitoneal injections of 88 mg/kg body weight of iron-dextran for 16 days. Tetracyclines were injected intraperitoneally to evaluate dynamic parameters of bone. Undecalcified histological sections of the tibiae were obtained. Serum urea, creatinine, and paratohormone (PTH) levels were evaluated 30 days after the onset of the experiment. Static and dynamic histomorphometric measurements were performed. Iron overload modified the response of the animals with renal failure: a reduction in bone forming activity compatible with adynamic bone disease and a decrease in peritrabecular fibrosis were observed. Our results suggest that iron is yet one more factor involved in the imbalance in bone metabolism typically found in renal failure patients treated with iron, rendering diagnosis and treatment of bone disease in these patients more complex.

Key Words: Rat tibia • iron overload • bone histomorphometry • renal failure • adynamic bone disease • bone remodeling

Abbreviations: RF, Renal failure • Io, Iron overload • RF+Io, Renal failure+iron overload • PTH, Parathyroid hormone • ABD, Adynamic bone disease • PN, Partial nephrectomy (left kidney) • TN, Total nephrectomy (right kidney) • Tc(1), 1st Injection of tetracycline (oxytetracycline) • Tc(2), 2nd Injection of tetracycline (demeclocycline)

Toxicologic Pathology, Vol. 33, No. 3, 398-403 (2005)
DOI: 10.1080/01926230590935826
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