title: Chronic cadmium treatment induces tubular nephropathy and osteomalacic osteopenia in ovariectomized cynomolgus monkeys.
abstract: 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.
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, Mitsubishi Chemical Medience Corporation, Kamisu, Ibaraki, Japan Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kurata
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, Mitsubishi Chemical Medience Corporation, Kamisu, Ibaraki, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Katsuta
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, Mitsubishi Chemical Medience Corporation, Kamisu, Ibaraki, Japan Doi.Takuya@mx.medience.co.jp.
authors.forename: T
authors.initials: T
authors.lastname: Doi
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, Mitsubishi Chemical Medience Corporation, Kamisu, Ibaraki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawasuso
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, Mitsubishi Chemical Medience Corporation, Kamisu, Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hiratsuka
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, Mitsubishi Chemical Medience Corporation, Kamisu, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsuchitani
authors.affiliation: Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Umemura
mesh_terms: D000818:Animals; D001835:Body Weight; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000503:physiopathology; D001842:Bone and Bones / Q000503:physiopathology; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008252:Macaca fascicularis; D008992:Monkey Diseases / Q000139:chemically induced* / Q000503:physiopathology; D010052:Ovariectomy; D010758:Phosphorus / Q000097:blood; D011897:Random Allocation; D016482:Urinalysis
chemical_list: D002104:Cadmium; D010758:Phosphorus
keywords: cadmium; chronic toxicosis; heavy metal toxicity; kidney; osteomalacic osteopenia; osteoporosis; primate; renal tubular nephropathy