STUDIES ON THE METABOLISM AND TOXICITY OF BUTYLTIN COMPOUNDS IN VIVO
| Project/Area Number |
12660291
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | Kitasato University |
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Principal Investigator |
UENO Shunji KITASATO UNIVERSITY VETERINARY MEDICINE ASSOCIATE PROFESSOR, 獣医畜産学部, 助教授 (70184950)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Takashi KYOTO PREFECTURAL UNIVERSITY HUMAN ENVIRONMENT PROFESSOR, 人間環境学部, 教授 (00132887)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| 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)
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| Keywords | organotin compounds / metabolism / hepatotoxicity / immunotoxicity / rodent / primates / mitochondria |
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| 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
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Report
(3 results)
Research Products
(15 results)
