TACROLIMUS (FK506)-INDUCED NEPHROTOXICITY IN SPONTANEOUS HYPERTENSIVE RATS
スポンサーリンク
概要
- 論文の詳細を見る
To clarify the profile of the tacrolimus (FK506)-induced nephrotoxicity and its mechanism, 1, 2 and 4 mg/kg/day of tacrolimus was administered intramuscularly (i.m.) to spontaneous hypertensive rats (SHR) for 2 weeks, and biochemical and pathological parameters were studied in the animals. The acute nephrotoxicity of tacrolimus was characterized as increase of blood urea nitrogen (BUN) and plasma creatinine (P-Cr) levels in the groups of 1 mg/kg/day and more, decrease of creatinine clearance (CCr) value in the groups of 2 mg/kg/day and more, and histopathologically luminal narrowing of the arteriole adjacent the glomerulus in the groups of 1 mg/kg/day and more. These changes were associated with an increase of plasma renin activity (PRA) and urinary thromboxane B_2 content and decrease of 6-keto-prostagrandinF_<1α> (6-keto-PGF_<1α>) content. Nilvadipine, which is one of the Ca^<2+> antagonist and is known to have renal vasodilating activity, prevented both biochemical and histopathological changes due to tacrolimus. The results indicated that the acute nephrotoxicity of tacrolimus was derived from impairment of glomerular function associated with the constriction of the renal arteriole brought about by the drug. All of these renal disorders induced by tacrolimus recovered completely or partially when the drug was withdrawn for 2 or 4 weeks. Consequently, the acute nephrotoxicity of tacrolimus in SHR was considered to be reversible.
- 日本トキシコロジー学会の論文
- 1994-11-30
著者
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OHARA Kaname
Toxicol. Res. Lab., Fujisawa Pharmaceutical Co., LTD.
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ISHIDA Hisao
Toxicol. Res. Labs. Fujisawa Pharmaceutical Co., Ltd.
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Ohara K
Toxicology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Ishida Hisao
Toxicol. Res. Labs. Fujisawa Pharmaceutical Co. Ltd.
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Ishida Hisao
Toxicology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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MITAMURA Takashi
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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YAMADA Atsushi
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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FUJIHIRA Shiro
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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NOGUCHI Hideyo
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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MINE Yasuhiro
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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MITAMURA Takashi
Advanced Science Research Laboratory, Saitama Institute of Tehnology
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Mine Y
Fujisawa Pharmaceutical Co. Ltd. Osaka Jpn
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Mine Yasuhiro
Toxicicology Research Laboratories Fujisawa Pharmaceutical Co.ltd.
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Fujihira Shiro
Toxicologic Pathology Drug Safety Research Labs. Astellas Pharma Inc.
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Fujihira Shiro
Toxicology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Mitamura Takashi
Drug Safety Res. Laboratories Astellas Pharma Inc.
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Mitamura Takashi
Drug Safety Research Laboratories Astellas Pharma Inc.
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Noguchi H
Daiich Pure Chemicals Co. Ltd. Tokyo Jpn
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Noguchi Hideyo
Toxicology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Yamada Atsushi
Drug Safety Res. Laboratories Astellas Pharma Inc.
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