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Assessment of the intestinal permeability and gastrointestinal toxicity by anticancer drugs

Research Project

Project/Area Number 13671365
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionFukuoka Dental College

Principal Investigator

INUTSUKA Sadaaki (2003)  Fukuoka Dental College, Surgery, Lecturer, 歯学部, 講師 (40258596)

是永 大輔 (2001-2002)  福岡歯科大学, 歯学部, 教授 (90170414)

Co-Investigator(Kenkyū-buntansha) HONDA Masayuki  Fukuoka Dental College, Surgery, Lecturer, 歯学部, 講師 (40330972)
安田 光宏  福岡歯科大学, 歯学部, 講師 (90269043)
犬塚 貞明  福岡歯科大学, 歯学部, 講師 (40258596)
野添 忠浩  福岡歯科大学, 歯学部, 講師 (90325457)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
KeywordsS-1 / Intestinal permeability / Chemotherapy / Oxonic acid / mannitol負荷試験 / オタスタットカリウム / Lactulose / Mannitol負荷試験 / 化学療法 / 副作用 / 腸管粘膜透過性 / Nitric oxide
Research Abstract

Although intestinal permeability is known to increase in conditions of stress (such as septic shock, and ischemia-reperfusion), the mechanism of gut barrier dysfunction during chemotherapy remains to be elucidated. We designed an experiment to assess the extent of damage or an increase in permeability of intestinal mucosa of rat after administration of anti cancer drugs.
Experiment 1 : The rats were given the anticancer drug after gastrectomy, and their intestinal permeability were estimated by an injection of FITC-dextran. A linear regression analysis revealed a positive significant correlation between FITC-dextran levels and plasma nitric oxide levels. When the anticancer drug was administrated, the mucosal atrophy and decreased expression of CD44 were revealed.
Experiment 2 : Rats were given S-1, new anticancer drug, which consists of tegafur, CDHP, and oxonic acid. The rats' intestinal permeability was determined by lactulose / mannitol test. The gastrointestinal toxicity resulting from administration of tegafur is accompanied by an impaired gut barrier function measurable as an increase in intestinal permeability to lactulose / mannnitol.
Experiment 3 : The serum SOD levels in rats were increased after administration of anticancer drugs. The serum SOD levels of patients who were suffering from gastric, colorectal or breast cancer were measured during chemotherapy. There correlation between prognosis of patients and increase of SOD levels were increase after chemotherapy.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Nagahama S, et al.: "Assessment of the intestinal permeability and the oral administration of anticancer drugs in rats : Nitric oxide release is response to gut injury."Surgery. 131. s92-s97 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Korenaga D, et al.: "Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue, tegaful, in rats."Eur Surg Res. 34. 351-356 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagahama S, Korenaga D, Honda M, Inutsuka S, Sugimach K: "Assessment of the intestinal permeability and the oral administration of anticancer drugs in rats : Nitric oxide release in response to gut injury."Surgery. 131. s92-s97 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Korenaga D, Honda M, Yasuda M, Inutsuka S, Nozoe T.: "Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue, tegaful, in rats."Eur.Surg.Res.. 34. 351-356 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagahama S, et al.: "Assessment of the intestinal permeability and the oral administration of anticancer drugs in rats : Nitric oxide release in response to gut injury."Surgery. 131. S92-S97 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Korenaga D, et al.: "Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue, tegaful, in rats."Eur Surg Res. 34. 351-356 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Nagahama et al.: "Assessment of the intestinal permeability and the oral administration of anticancer drugs in rats : Nitric oxide release in response to gut injury"Surgery. 131. S92-S97 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] D.Korenaga et al.: "Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue, tegaful, in rats"Eur Surg Res. 4. 351-356 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ngahama S, Korenaga D, Honda M et al.: "Assessment of the intestinal permeability after a gastrectomy and the oral administration of anti-cancer drugs in rats : Nitric oxide release in response to gut injury"Surgery. 131巻1号. S92-S97 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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