Regulation of renal organic ion transporters in cisplatin-induced acute kidney injury and uremia in rats

• Morisaki, Takafumi

• Matsuzaki, Takanobu

• Yokoo, Koji

• Kusumoto, Masahiro

• Iwata, Kazufumi

• Hamada, Akinobu

• Saito, Hideyuki

• 森崎, 崇文

• 松崎, 尊信

• 横尾, 浩司

• 楠本, 将裕

• 岩田, 一史

• 濱田, 哲暢

• 齋藤, 秀之

抄録

type:論文(Article)

Purpose The purpose of this study was to examine the regulation of renal organic ion transporters in cisplatin-induced acute kidney injury (AKI) and its relation with indoxyl sulfate (IS), a uremic toxin. Methods The IS concentrations in the serum and kidney were monitored by high-performance liquid chromatography. Uptake of p-aminohippuric acid, estrone-3-sulfate and tetraethylammonium were examined using renal slices. Real-time PCR and immunoblotting were performed to examine the mRNA and protein expression of rOATs, rOCTs and rMATE1 in the kidney, respectively. Results The serum and renal IS levels were markedly elevated in cisplatin-treated rats. However, this effect was largely reversed by administration of AST-120, an oral charcoal adsorbent. The functions of renal basolateral organic anion and cation transporters were reduced in cisplatin-treated rats. The levels of mRNA and protein corresponding to rOAT1, rOAT3, rOCT2 and rMATE1, but not rOCT1, were depressed in the kidney of cisplatin-treated rats. Administration of AST-120 to cisplatin-treated rats partially restored the function and expression level of these transporters. Conclusions Cisplatin-induced AKI causes down-regulation of renal organic ion transporters accompanied by accumulation of serum and renal IS. IS could be involved in the mechanism of down-regulation of rOAT1, rOAT3 and rMATE1 under cisplatin-induced AKI.

source:07248741

identifier:http://www.springerlink.com/content/t244462842j0v631/

収録刊行物

• Pharmaceutical Research

  Pharmaceutical Research 25 (11), 2526-2533, 2008-07-09

  Springer Netherlands

キーワード

• acute kidney injury
• cisplatin
• indoxyl sulfate
• organic anion transporter
• organic cation transporter
• 491.5
• 491.65

詳細情報

• CRID: 1050564287880386176
• NII論文ID: 120002469602
• Web Site: http://hdl.handle.net/2298/15509
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles
  • KAKEN