TY - JOUR
T1 - Chronic Cadmium Treatment Induces Tubular Nephropathy and Osteomalacic Osteopenia in Ovariectomized Cynomolgus Monkeys
AU - Kurata, Y.
AU - Katsuta, O.
AU - Doi, T.
AU - Kawasuso, T.
AU - Hiratsuka, H.
AU - Tsuchitani, M.
AU - Umemura, T.
N1 - Funding Information:
The author(s) declared receipt of the following financial support for the research, authorship, and/or publication of this article. This study was supported financially in part by the Japanese Enviromental Agency.
PY - 2014/9
Y1 - 2014/9
N2 - In an attempt to establish a primate model of chronic cadmium toxicosis, we ovariectomized cynomolgus monkeys and treated them with CdCl2 by repeated intravenous injections for 13 to 15 months. The animals showed normocytic-normochromic anemia. The cadmium treatment resulted in increases of urinary enzyme activity indicative of renal tubular degeneration. Histopathology of the kidney revealed renal proximal tubular atrophy accompanied by interstitial fibrosis. Decreased bone mineral density was evident in the trabecular and cortical zones of the lumbar vertebra and femur, with osteoid accumulation around the trabeculae and Haversian canals. Iron deposition at the mineralization front and osteoclasts hyperplasia were indicative of impairment of bone mineralization and an increase of resorption. Blood inorganic phosphorus and 1α,25(OH)2 vitamin D3 levels decreased and urinary deoxypyridinoline level increased in cadmium-treated animals. The renal and bone lesions closely resemble those of itai-itai disease patients, the most severe case of cadmium toxicosis in terms of clinical chemistry and histopathology. Thus, ovariectomized monkeys chronically exposed to cadmium can serve as a primate itai-itai disease model, which is beneficial for developing novel therapeutic methods, investigating the mechanisms of the renal and bone lesions, and establishing more clearly defined criteria for diagnosing the disease.
AB - In an attempt to establish a primate model of chronic cadmium toxicosis, we ovariectomized cynomolgus monkeys and treated them with CdCl2 by repeated intravenous injections for 13 to 15 months. The animals showed normocytic-normochromic anemia. The cadmium treatment resulted in increases of urinary enzyme activity indicative of renal tubular degeneration. Histopathology of the kidney revealed renal proximal tubular atrophy accompanied by interstitial fibrosis. Decreased bone mineral density was evident in the trabecular and cortical zones of the lumbar vertebra and femur, with osteoid accumulation around the trabeculae and Haversian canals. Iron deposition at the mineralization front and osteoclasts hyperplasia were indicative of impairment of bone mineralization and an increase of resorption. Blood inorganic phosphorus and 1α,25(OH)2 vitamin D3 levels decreased and urinary deoxypyridinoline level increased in cadmium-treated animals. The renal and bone lesions closely resemble those of itai-itai disease patients, the most severe case of cadmium toxicosis in terms of clinical chemistry and histopathology. Thus, ovariectomized monkeys chronically exposed to cadmium can serve as a primate itai-itai disease model, which is beneficial for developing novel therapeutic methods, investigating the mechanisms of the renal and bone lesions, and establishing more clearly defined criteria for diagnosing the disease.
KW - cadmium
KW - chronic toxicosis
KW - heavy metal toxicity
KW - kidney
KW - osteomalacic osteopenia
KW - osteoporosis
KW - primate
KW - renal tubular nephropathy
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U2 - 10.1177/0300985813509384
DO - 10.1177/0300985813509384
M3 - Article
C2 - 24165203
AN - SCOPUS:84906348668
SN - 0300-9858
VL - 51
SP - 919
EP - 931
JO - Pathologia veterinaria
JF - Pathologia veterinaria
IS - 5
ER -