A new insight into the mechanism of dioxin toxicity: relevance of leukotrien B4 accumulation to toxcity and Yusho incident
| Project/Area Number |
24659053
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Environmental pharmacy
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| Research Institution | Kyushu University |
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Principal Investigator |
YAMADA Hideyuki 九州大学, 薬学研究科(研究院), 教授 (40142351)
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| Co-Investigator(Renkei-kenkyūsha) |
FURUE Masutaka (70134583)
UCHI Hiroshi (50437787)
TAKEDA Tomoki (60596831)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ダイオキシン / ロイコトリエンB4 / 5-リポキシゲナーゼ / メタボロミクス / 芳香族炭化水素受容体 / メタボローム |
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| Research Abstract |
A reduction in hepatic leukotrien B4 (LTB4) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in rats and mice. The results showed that this alteration is caused by a combination of the increased expression of 5-lipoxygenase (5-LOX), a precursor-synthesizing enzyme, and the reduced expression of leukotrien C4 synthase, a enzyme which leads the precursor to the different pathway. The aryl hydrocarbon receptor (Ahr) is suggested to play a role in 5-LOX induction. This is because 5-LOX induction occurred at fewer TCDD doses in C57BL/6J mice expressing Ahr with high affinity to TCDD than in DBA/2J mice with low affinity Ahr. LTB4 is an inflammatory factor. This mediator draws neutrophils expressing myeloperoxidase (MPO) the products of which serve in cell-killing effects. In accordance with this, TCDD increased the hepatic level of MPO.
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Report
(3 results)
Research Products
(11 results)
