role of endoplasmic reticulum stress in acetaminophen-induced liver injury
Project/Area Number |
23790603
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Applied pharmacology
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Research Institution | Kumamoto University |
Principal Investigator |
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 小胞体ストレス / アセトアミノフェン / 肝障害 / 有害事象 / フェニル酪酸 / 4-phenylbutyrate / 4-PBA / CHOP / 薬剤性肝傷害 / 医薬品副作用 / 医薬品有害事象 |
Research Abstract |
This study was conducted to evaluate the role of endoplasmic reticulum (ER) stress in acetaminophen-induced liver injury in mice. We demonstrated the hepatic Xbp1 mRNA splicing induction by APAP injection using ERAI (ER stress activated indicator) transgenic mice. In addition, we proved that C/EBP homologous protein, an ER stress related-transcriptional factor, null mice were protected from APAP induced hepatotoxicity compared with wild-type mice. Furthermore, we also found that 4-phenylbutyric acid (4-PBA), an ER stress suppressor, significantly attenuated the APAP-induced liver injury in mice. These results indicate that ER stress plays important role in the development of APAP hepatotoxicity in mice, and suggest that ER stress suppression is a promising therapeutic strategy against APAP-induced liver injury.
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] Influence of Npc1 genotype on the toxicity of hydroxypropyl -β-cyclodextrin, a potentially therapeutic agent, in Niemann-Pick Type C disease models2014
Author(s)
Tanaka Y, Ishitsuka Y, Yamada Y, Kondo Y, Takeo T, Nakagata N, Higashi T, Motoyama K, Arima H, Matsuo M, Higaki K, Ohno K, Irie T
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Journal Title
Molecular Genetics and Metabolism Reports
Volume: 1
Pages: 31-41
DOI
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Peer Reviewed
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[Journal Article] Comparative effects of phosphoenolpyruvate (PEP), a glycolytic intermediate, as an organ preservation agent with glucose and N-acetylcysteine against organ damage during cold storage of mouse liver and kidney2013
Author(s)
Ishitsuka Y, Fukumoto Y, Kondo Y, Irikura M, Kadowaki D, Narita Y, Hirata S, Moriuchi H, Maruyama T, Hamasak N, Irie T
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Journal Title
ISRN Pharmacology
Volume: 2013
Pages: 375825-375825
DOI
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Peer Reviewed
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[Journal Article] Phosphoenolpyruvic acid (PEP), an intermediary metabolite of glycolysis, as a potential cytoprotectant and anti-oxidant in HeLa cells2012
Author(s)
Kondo Y and Ishitsuka Y, Kadowaki D, Kuroda M, Tanaka Y, Nagatome M, Irikura M, Hirata S, Sato K, Maruyama T, Hamasaki N, and Irie T
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 35
Pages: 606-611
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Peer Reviewed
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[Presentation] 高用量アセトアミノフェン坐剤の製剤特性およびその有効性・安全性に関する研究2012
Author(s)
石塚洋一,竹浦宏幸,田添光二,野田寛子,入倉充,永田浩泰,秋吉明子,陣上祥子,吉田稔,福永栄子,入江徹美
Organizer
第15回日本医薬品情報学会総会・学術大会
Place of Presentation
東大阪、近畿大学
Year and Date
2012-07-08
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