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Investigative study of drug-induced nephropathy using renal cortical slice technique and cultured cell line

Research Project

Project/Area Number 08671822
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

UOZUMI Jiro  Kyushu University, Faculty of Medicine, Department of Urology, Assistant Professor, 医学部, 講師 (30223514)

Co-Investigator(Kenkyū-buntansha) TOKUDA Noriaki  Kyushu University, Faculty of Medicine, Department of Urology, Assistant Profess, 医学部, 助手 (20264038)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Keywordsantibiotics / cisplatin / contrast medium / methylprednisolone / drug-induced nephropathy / NAG / gamma-GTP / renal cortical slice / イオン性造影剤 / 非イオン性造影剤 / r-GTP / 腎組織スライス / 抗癌剤
Research Abstract

Experimental study to investigate the mechanism of prophylactic effect of methylprednisolone on cisplatin nephrotoxicity and clinical study to confirm the protective effects of methylprednisolone against cisplatin nephrotoxicity were conducted. Methylprednisolone induced increase in urinary platinum excretion, accompanied by a decrease in kidney platinum concentrations. The clinical usefulness of methylprednisolone against cisplatin nephrotoxicity were indicated.
Renal cortical tissue prepared from rat and human were sliced and incubated with cefaloridine (CER) or gentamicin (GM) to examine the usefulness of renal cortical slice techniques. NAG was released from rat renal slice dose-dependently on CER concentration. Dose-related release of gamma-GTP from rat renal slice incubated with CER was not found. NAG release from human kidney tissue incubated with CER were less compared with that from rat kidney tissue. Human kidney tissue was less sensitive to CER nephrotoxicity. GM did not sign … More ificantly affect the enzyme release either from rat or human renal slice. This in vitro system is a simple and economical assay system to evaluate the drug-induced nephrotoxicity.
The usefulness of renal cortical slice technique as an in vitro assay system to detect drug-induced nephrotoxicity was studied by evaluating the renal toxicity of cisplatin. Dose dependent increases of NAG, gamma-GTP, and LDH were observed. PAH accumulation in kidney slices was significantly reduced by cisplatin. Inhibitory effect of cisplatin on gluconeogenesis in renal slices was observed. These results suggested that toxic effect of cisplatin on renal epithelial cells was quantitatively determined by renal cortical slice technique. Renal cortical slice technique is a simple and economical in vitro assay system for evaluating cisplatin nephrotoxicity.
To evaluate the contrast medium nephropathy, nephrotoxicity of low-osmolality contrast medium (LOOM) were examined in patients received radiographic studies using nonionic LOOM.Nephrotoxic effects of LOOM were compared with those of ionic high-osmolality contrast medium (HOOM) by renal cortical slice technique using rat renal tissue. Urinary NAG and gamma-GTP were sensitive indicators for contrast medium nephropathy. The clinical investigation suggested that nonionic LOOM injured renal tubular cells, while those renal damage can not be detected by serum creatinine or creatinine clearance. Renal cortical slice technique revealed that nonionic LOOM was as nephrotoxic as ionic HOCM. Less

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Uozumi J: "The effect of methylprednisolone on platinum kinetics and urinary enzyme excretion following intravenous cisplatin in vivo and on the growth inhibition of LLC-PK1 cells by cisplatin in vitro" Res Exp Med. 196・4. 211-217 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J: "The protective effect of methylprednisolone against cisplatin-induced nephrotoxicity in patients with urothelial tumors" Int J Urol. 3・5. 343-347 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 魚住二郎: "MVAC動注と全身投与におけるシスプラチン投与後の腎機能変化の比較検討" 西日泌尿. 59・5. 438-441 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J: "The evaluation of drug-induced nephrotoxicity using renal cortical slice obtained from rat and human" Brit J Urol. 80・suppl 2. 116 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakamura M: "Renal cotical slice techniques for evaluating drug-induced nephrotoxicity in rat and human" Toxicol Letters. 95・suppl 1. 166 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J: "Contrast medium nephropathy caused by nonionic low-osmolarity contrast materials" Toxicol Letters. 95・suppl 1. 116-167 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J,Koikawa Y,Yasumasu T,Ueda T,Tokuda N,Kumazawa J: "The effect of methylprednisolone on platinum kinetics and urinary enzymes excretion following intravenous cisplatin in vivo and on the growth inhibition of LLC-PK1 cells by cisplatin in vitro." Res Exp Med. 196-4. 211-217 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J,Koikawa Y,Tokuda N,Yasumasu T,Kumazawa J: "The protective effect ofmethylprednisolone against cisplatin-induced nephrotoxicity in patients with urothelial tumors." Int J Urol. 3-5. 343-347 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J,Tokuda N,Nakamura M,Naito S,Kumazawa J: "Comparative study concerning the nephrotoxic effects of cisplatin following intra-arterial MVAC and systemic MVAC therapy (Japanese)" Nishinihon J Urol. 59-5. 438-441 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J,Kumazawa J,Nakamura M: "The evaluation of drug-induced nephrotoxicity using renal cortical slice obtained from rat and human." Brit J Urol. 80-suppl 2. 116 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakamura M,Uozumi J: "Renal corticl slice techniques for evaluating drug-induced nephrotoxicity in rat and human." Toxicol Letters. 95-suppl 1. 166 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J,Nakamura M: "Contrast medium nephropathy caused by nonionic low-osmolality contrast materials." Toxicol Letters. 95-suppl 1. 166-167 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uozumi J: "The effect of methylprednisolone on plainum kinetics and urinary enzyme excreion following intravenous cisplatin in vivo and on the growth inhibition of LLC-PKI cells by cisplatin in vitro" Res Exp Med. 196・4. 211-217 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uozumi J: "The protective effect of methylprednisolone against cisplatin-induced nephrotoxicity in patients with urothelial tumors" Int Urol. 3・5. 343-347 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] 魚住二郎: "MVAC動注と全身投与におけるシスプラチン投与後の腎機能本科の比較検討" 西日泌尿. 59・5. 438-441 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uozumi J: "The evaluation of drug-induced nephrotoxicity using renal cortical slice obtained from rat and human" Brit J Urol. 80・suppl 2. 116 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakamura M: "Renal cotical slice techniques for evaluating drug-induced nephrotoxicity in rat and human" Toxicol Letters. 95・suppl 1. 166 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uozumi J: "Contrast medium nephropathy caused by nonionic low-osmolarity contrast materials" Toxicol Letters. 95・suppl 1. 166-167 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jiro Uozumi et al: "The effect of methylprednisolone on platinum kinetics an urinary enzyme excretion following intravenous cisplatin in vivo and on the growth inhibition of LLC-PK1 cells by cisplatin in vitro" Res Exp Med. 196. 211-217 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Jiro Uozumi et al: "The protective effect of methylprednisolone against cisplatin-induced nephrotoxicity in patients with urothelial tumors" Int J Urol. 3. 343-347 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Jiro Uozumi et al: "The effect of methylprednisolone on platinum kinetics and urinary enzyme excretion following intravenous cisplatin in vivo and on the growth inhibition of LLC-PK1 cells by cisplatin in vitro" Res Exp Med. 196. 211-217 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jiro Uozumi et al: "The protective effect of methylprednisolone against cisplatin-induced nephrotoxicity in patients with urothelial tumors" Int J Urol. 3. 343-347

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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