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STUDIES ON THE METABOLISM AND TOXICITY OF BUTYLTIN COMPOUNDS IN VIVO

Research Project

Project/Area Number 12660291
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionKitasato University

Principal Investigator

UENO Shunji  KITASATO UNIVERSITY VETERINARY MEDICINE ASSOCIATE PROFESSOR, 獣医畜産学部, 助教授 (70184950)

Co-Investigator(Kenkyū-buntansha) SUZUKI Takashi  KYOTO PREFECTURAL UNIVERSITY HUMAN ENVIRONMENT PROFESSOR, 人間環境学部, 教授 (00132887)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordsorganotin compounds / metabolism / hepatotoxicity / immunotoxicity / rodent / primates / mitochondria
Research Abstract

One aim of this project was to elucidate the mechanism of hepatotoxicity of butyltin compounds in Rodentia in vivo. Furthermore, the toxicity and metabolism of butyltin compounds were also observed in the cynomolgus monkeys, in order to estimate the risk of these compounds as a food contaminant to human.
1. The difference in hepatotoxicity of butyltin compounds between mice and guinea pigs.
Tributyltin chloride (TBTC) and dibutyltin dichloride (DBTC) could induce the obvious liver injury in mice, but guinea pigs. TBTC was metabolized to DBTC as the main metabolite, however DBTC was hardly degraded in the livers of both animals. Distributions of DBTC in the mitochondrial fractions of hepatocytes were higher in mice than in guinea pigs. These results suggested that the variations in hepatotoxicity among the species might partly arise from the different distribution of DBTC on the cell organelles, especially mitochondria.
2. Effects of butyltin compounds in the mitochondrial respiration in v … More ivo and in vitro.
TBTC and DBTC could induce the damage in mitochondria of hepatocytes only in mice, but guinea pigs in vivo. Although there was no significant difference in the IC_<50> of TBTC or DBTC against the mitochondrial state 3 respiration of hepatocytes in vitro between mice and guinea pigs, the mitochondrial respiration had been remarkably inhibited only in the liver of mice administered with TBTC or DBTC in vivo. The contents of DBTC in the mitochondrial fractions of hepatocytes were higher in the mice compared with guinea pigs at 24 hr after TBTC or DBTC. These results suggested that the severe hepatotoxicities of TBTC or DBTC in mice in vivo were induced by the depression of raitochondrial function by DBTC, and caused by the high affinity for DBTC of mitochondrial fractions in mice hepatocytes.
3. Toxicity of butyltin compounds on Primate
TBTC could induce the obvious sublymphemia, and increase of some serodiagnostic indexes indicating kidney and liver injury in cynomolgus monkey. DBTC could not induce any distinctive influence in hemodiagnosis and serodiagnosis in the monkey, except for the remarkable atrophy in thymus. TBTC was metabolized to DBTC (69%) and raonobutyltin trichloride (MBTC) (21%), however 99% of butyltins was detected as DBTC in the liver of DBTC treated animal. These results suggested that TBTC and DBTC might be toxic for Primates including human. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] UENO, S. et al.: "Butyltin and phenyltin compounds in some marine products on the Japanese market"Archives of Environmental Health. 54. 20-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Effect of SKF-525A on liver metabolism and hepatotoxicity of tri-and dibutyltin compounds in mice"Archives of Toxicology. 71. 513-518 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Role of cytochrome P450 in hepatotoxicity induced by di-and tributyltin compounds in mice"Archives of Toxicology. 69. 655-658 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Determination of butyltin metabolites in the mouse liver by flameless atomic absorption spectrophotometry"Journal of Veterinary Medical Science. 57. 789-791 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Comparison of hepatotoxicity caused by mono-, di-and tributyltin compounds in mice"Archives of Toxicology. 69. 30-34 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Butyltin and phenyltin compounds in some marine products on the Japanese market"Archives of Environmental Health. 54. 20-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Effect of SKF-525A on liver metabolism and he patotoxicity of tri- and dibutyltin compounds in mice"Archives of Toxicology. 71. 513-518 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Role of cytochrome P450 in hepatotoxicity indu ced by di- and tributyltin compounds in mice"Archives of Toxicology. 69. 655-658 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Determination of butyltin metabolites in the mo use liver by flameless atomic absorption spectro photometry"Journal of Veterinary Medical Science. 57. 789-791 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Comparison of hepatotoxicity caused by mono- di- and tributyltin compounds in mice"Archives of Toxicology. 69. 30-34 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] UENO, S. et al.: "Butyltin and phenyltin compounds in some marine products on the Japanese market"Archives of Environmental Health. 54. 20-25 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] UENO, S. et al.: "Effect of SKF-525A on liver metabolism and hepatotoxicity of tri-and dibutyltin compounds in mice"Archives of Toxicology. 71. 513-518 (1997)

    • Related Report
      2001 Annual Research Report
  • [Publications] UENO, S. et al.: "Role of cytochrome P450 in hepatotoxicity induced by di-and tributyltin compounds in mice"Archives of Toxixology. 69. 655-658 (1995)

    • Related Report
      2001 Annual Research Report
  • [Publications] UENO, S. et al.: "Determination of butyltin metabolites in the mouse liver by flameless atomic absorption spectrophotometry"Journal of Veterinary Medical Science. 57. 789-791 (1995)

    • Related Report
      2001 Annual Research Report
  • [Publications] UENO, S. et al.: "Comparison of hepatotoxicity caused by mono-, di-and tributyltin compounds in mice"Archives of Toxicology. 69. 30-34 (1994)

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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