The involvement of dihydropyrazine-induced gene damage in diabetic complication
| Project/Area Number |
23590160
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | Sojo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKECHI Shinji 崇城大学, 薬学部, 教授 (10222100)
YAMAGUCHI Tadatoshi 崇城大学, 薬学部, 教授 (80037598)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ジヒドロピラジン / 糖化反応 / 毒性 / 酸化的ストレス / 糖尿病 / 細胞障害 / HepG2 細胞 / ジヒドロピラジン類 / 細胞障害性 / グルタチオンバランス / 糖化反応中間体 / 遺伝子障害 |
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| Research Abstract |
Dihydropyrazines (DHPs), formed by nonenzymatic glycation, are known to exert various effects in vitro and in vivo. In this study, we investigated the effects of DHP on human hepatoma HepG2 cells using 2,3-dihydro-5,6-dimethylpyrazine (DHP-1), 2,3-dihydro-2,5,6-trimethylpyrazine (DHP-2), and 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3) as model compounds. All of the tested compounds exerted cytotoxic activity against HepG2 cells, and significantly so at the highest concentration. DHP-3 was the most cytotoxic drug. Additionally, DHP-3 exposure showed the significant increase of heme oxygenase-1 and glutamate cysteine ligase catalytic subunit mRNA after exposure. The serum concentration of DHPs in diabetic patient showed significant increase compared with that in non-diabetic patient. Therefore, These results suggested that the Nrf2-ARE signal pathway activated by oxidative stress is in part involved in the effect of DHP on mammalian cells.
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Report
(4 results)
Research Products
(10 results)
