LONG-TERM, LOW-DOSE, CADMIUM-INDUCED NEPHROPATHY WITH RENAL OSTEOPATHY IN OVARIECTOMIZED RATS
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概要
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To establish an animal model of chronic cadmium nephropathy and osteopathy, we intraperitoneally administered 0.228 mg CdCl_2 (Cd) or normal saline (NS) to 52 female Sprague-Dawley (S.D.) rats 3 times a week for 16 months following ovariectomy (OV) or sham surgery (Sham), dividing the animals into three experimental groups (OV-Cd, Sham-Cd and OV-NS). Two groups of male S.D. rats were also administered Cd or NS (22 animals; Male-Cd and Male-NS). Cd-administered rats gained significantly less body weight than NS rats after 16months of experiments with no signs of emaciation. Serum creatinine levels and Cd contents in the kidney had significantly increased in the Cd-administered rats. OV-Cd rats showed significant decreases in PTH levels and increases in calcium contents in the kidney and other organs. Kidneys of Cd-administered rats showed atrophy, dilatation, and interstitial fibrosis of tubules. Sclerosis and collapse of the glomeruli were observed in the Cd groups with no proliferation in mesangial cells or matrix. The Haversian canal system of the Cd-administered rats disappeared and was replaced by a large quantity of degenerated, necrotic, and restorative tissues. Bone histomorphometric parameters showed that osteoid volume and osteoid surface had significantly increased in the Male-Cd group. In contrast, decreases in bone mass and increases in fibrous tissue were found to be more prominent in the OV-Cd group. Our results have demonstrated for the first time that long-term, 1ow-dose CdCl_2 administration to ovariectomized S.D. rats is capable of inducing irreversible nephropathy with osteopathy exhibiting pathological and bone histomorphometric characteristics that are very similar to those of Itai-Itai disease.
- 日本トキシコロジー学会の論文
- 1997-08-10
著者
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Marumo Fumiaki
Department of Internal Medicine, Kitasato University School of Medicine
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Akiba Takashi
Department Of Medicine Kidney Center Tokyo Women's Medical University
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Li Jing
Department Of Pharmacology Marine Drug And Food Institute Ocean University Of China
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Akashi Takumi
Department Of Clinical Pathology Graduate School Of Medicine Tokyo Medical And Dental University
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Akiba T
Kowa Co. Ltd. Shizuoka Jpn
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Akiba Takashi
Department Of Blood Purification Tokyo Women's Medical University
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Akiba Takashi
Kidney Center Tokyo Medical And Dental University
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Akiba Tomohide
Dept. Of Toxicology Fuji Research Laboratoris Kowa Co. Ltd.
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Marumo F
Tokyo Medical And Dental Univ. Tokyo Jpn
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Marumo Fumiaki
Department Of Clinical And Molecular Endocrinology Graduate School Tokyo Medical And Dental Universi
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Marumo Fumiaki
Department Of Blood Purification Tokyo Medical And Dental University
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Marumo Fumiaki
Kidney Center Tokyo Medical And Dental University
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Akiba Takashi
The Second Department Of Internal Medicine Tokyo Medical And Dental University School Of Medicine
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Li Jing
Department Of Internal Medicine Tokyo Medical And Dental University
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Akizawa Tadao
Center Of Blood Purification Therapy Wakayama Medical School
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Takeshita Akira
From Reseach Institute Of Angiocardiology And Cardiovascular Clinic Faculty Of Medicine Kyushu Unive
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Asai Tomoki
Department Of Homeostasis Medicine And Nephrology Tokyo Medical And Dental University Graduate Schoo
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Akiba Takashi
Department Of Blood Purification And Department Of Urology Tokyo Medical And Dental University
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Li Jing
Department Of Agriculture Faculty Of Agriculture Kochi University
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