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Lethal Toxicity of NSAID in BRM Primed Mice

Research Project

Project/Area Number 10672059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

OHNO Naohito  Tokyo University of Pharmacy and Life Science School of Pharmacy Associate Professor, 薬学部, 助教授 (80152213)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordsβ-glucan / BRM / NSAID / Lethal toxicity / Indomethacin / Interferon-γ / Macrophage / マクロファージ / β-グルカン / Bグルカン
Research Abstract

(1→3)-β-D-glucan (β-glucan) is a biological response modifier (BRM) that regulates host immune response. However, the side effects of this drug have not been extensively examined. In this study, we found that the combination of a β-glucan and a nonsteroidal anti-inflammatory drugs, indomethacin (IND), induced lethal toxicity in mice. Lethal toxicity of orally administered IND (multiple administration to ICR mice ; once a day of 2 weeks) was 0/8 (2.5 mg/kg) and 5/8 (5 mg/kg) (death/total) over 2 weeks. The toxicity was enhanced to 3/8 and 8/8 in mice treated with a clinical β-glucan preparation, sonifilan (250μg/mouse, single I.p. administration on day 0). Enhanced lethal toxicity resulted from a single p.o. administration of IND on day 5 to 9 after multiple β-glucans administration. A similar effect was observed for other β-glucans including,SSG,grifolan,zymosan A and zymocel. A similar effect was also observed for various microbial products, such as whole cell preparation of bacteria and fungi, BCG and OK-432. The lethal toxicity was shown by various strains of mice, such as C3H/HeN, C3H/HeJ, AKR/N, BALB/c, C57BL/6, DBA/2, BALB/c nu/nu, KSN, WBB6F1, and by various NSAIDs, such as aspirin, diclofenac, and sulindac. IFN-γ, IL-6 and CSF concentrations in sera of IND/β-glucan treated mice were significantly elevated. These results strongly suggest that IND/BRM treatment induces lethality in mice by mal-adjusting the cytokine network.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] N, Ohno et al: "Inflammatory and immunophormacological activities of metaperiodate oxidized zymosan"Zent, bl. Bakteriol.. 289. 63-77 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Miura et al: "Antigen Specific response of murine immune system toward a yeast β-glucan preparation, zymosan"FEMS Immunol. Med. Microb.. 24. 131-139 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A. Tsuzuki et al: "Interleukin 8 production of human leukocytes stimulated by triple or single helical conformation of an antifumor(1→3)β-glucan preparation, sonfilan"Drug. Develop. Res.. 48. 17-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Ohno, T.Miura, N.N.Miura, N.Chiba, M.Uchiyama, Y.Adachi, and T.Yadomae: "Inflammatory and Immunopharmacological activities of meta-periodate oxidized zymosan"Zent.bl.Bakteriol. 289. 63-77 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Miura, N.Ohno, N.N.Miura, Y.Adachi, S.Shimada, and T.Yadomae: "Antigen specific response of murine immune system toward a yeast β-glucan preparation, zymosan"FEMS Immunol.Med.Microb.. 24. 131-139 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A.Tsuzuki, N.Ohno, Y.Adachi, and T.Yadomae: "Interleukin 8 production of human leukocytes stimulated by triple or single helical conformer of an antitumor (1 β-D-glucan preparation, sonifilan)"Drug Develop.Res.. 48. 17-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Ohno et al: "Inflammatory and immunopharmacological activities of metaperiodate oxidized zymosan"Zent,bl.Bakterial. 289. 63-77 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Miura et al: "Antiqen specific response of murine immune system toward a yeast β-qlucan preparation,zymosan"FEMS Immunol,Med,Microb.. 24. 131-139 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Tsuzuki et al: "Interleukin 8 production of human leukocytes stimulated by triple or single helical conformer of an antitumos(1→3)-β-D-glucan preparation,sonifilan"Drg.Develop.Res.. 48. 17-25 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aiko Tsuzuki: "Increase of hematopcietic responses by triple or single helical conformer of an antitumor (1→3)-B-D-glucan preparation,sunifilan,in cydophosphamine-induced keukopenic mice" Biosci,Biotechnal.Biochem.,. 63(1). 104-110 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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