2013 Fiscal Year Final Research Report
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 |
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| Research Field |
Applied pharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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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 |
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| 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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[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
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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