L-Type Fatty Acid Binding Protein Transgenic Mouse as a Novel Tool to Explore Cytotoxicity to Renal Proximal Tubules

• NAKAMURA Kazuo

  CMIC Co. Ltd.

• ITO Kimihiro

  Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University

• KATO Yukio

  Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University

• SUGAYA Takeshi

  CMIC Co. Ltd.

• KUBO Yoshiyuki

  Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University

• TSUJI Akira

  Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University

Abstract

  A novel biomarker of renal dysfunction, liver-type fatty acid binding protein (L-FABP), which is expressed in human proximal tubules, binds to lipid peroxidation products during renal injury and is excreted into the urine. Here, we examined the usefulness of human L-FABP transgenic (Tg) mice as a tool to explore nephrotoxicity, employing two model drugs, cephaloridine and cisplatin, which are taken up by renal tubules via organic anion and cation transporters, respectively. Urinary excretion of L-FABP increased after administration of cephaloridine in most of the Tg mice, whereas glomerular filtration markers such as blood-urea-nitrogen (BUN) and plasma creatinine (CRE) were almost unchanged. Thus, L-FABP is a highly sensitive detector of the nephrotoxicity of cephaloridine. Urinary excretion of L-FABP in the Tg mice also increased after administration of cisplatin, and this increase was reduced by coadministration of cimetidine. Both BUN and CRE also increased after the cisplatin treatment, but these parameters were minimally affected by coadministration of cimetidine, suggesting that cimetidine reduces cisplatin-induced renal tubular toxicity with only a minimal effect on the glomerulus. These results indicate that the L-FABP Tg mouse should be a useful drug screening system to evaluate specifically the toxicity of transporter substrates to renal tubules.<br>

Journal

• Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Pharmacokinetics 23 (4), 271-278, 2008

  The Japanese Society for the Study of Xenobiotics

Keywords

• Transporters
• nephrotoxicity
• proximal tubules
• drug screening

Details

• CRID: 1390001205181074560
• NII Article ID: 10021956357
• NII Book ID: AA1162652X
• DOI: 10.2133/dmpk.23.271
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301968?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301968?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2009059458
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed