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Establishment of a mouse model of enalapril-induced liver injury and investigation of the pathogenesis
http://hdl.handle.net/2237/27027
http://hdl.handle.net/2237/27027e1ff7ed8-16aa-4fca-8274-b4d3c0bfb518
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-10 | |||||
タイトル | ||||||
タイトル | Establishment of a mouse model of enalapril-induced liver injury and investigation of the pathogenesis | |||||
言語 | en | |||||
著者 |
Shirai, Yuji
× Shirai, Yuji× Oda, Shingo× Makino, Sayaka× Tsuneyama, Koichi× Yokoi, Tsuyoshi |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
抄録 | ||||||
内容記述 | Drug-induced liver injury (DILI) is a major concern in drug development and clinical drug therapy. Since the underlying mechanisms of DILI have not been fully understood in most cases, elucidation of the hepatotoxic mechanisms of drugs is expected. Although enalapril (ELP), an angiotensin-converting enzyme inhibitor, has been reported to cause liver injuries with a low incidence in humans, the precise mechanisms by which ELP causes liver injury remains unknown. In this study, we established a mouse model of ELP-induced liver injury and analyzed the mechanisms of its hepatotoxicity. Mice that were administered ELP alone did not develop liver injury, and mice that were pretreated with a synthetic glucocorticoid dexamethasone (DEX) and a glutathione synthesis inhibitor l-buthionine-(S,R)-sulfoximine (BSO) exhibited liver steatosis without significant increase in plasma alanine aminotransferase (ALT). In mice pretreated with DEX and BSO, ALT levels were significantly increased after ELP administration, suggesting that hepatic steatosis sensitized the liver to ELP hepatotoxicity. An immunohistochemical analysis showed that the numbers of myeloperoxidase-positive cells that infiltrated the liver were significantly increased in the mice administered DEX/BSO/ELP. The levels of oxidative stress-related factors, including hepatic heme oxygenase-1, serum hydrogen peroxide and hepatic malondialdehyde, were elevated in the mice administered DEX/BSO/ELP. The involvement of oxidative stress in ELP-induced liver injury was further supported by the observation that tempol, an antioxidant agent, ameliorated ELP-induced liver injury. In conclusion, we successfully established a model of ELP-induced liver injury in DEX-treated steatotic mice and demonstrated that oxidative stress and neutrophil infiltration are involved in the pathogenesis of ELP-induced liver injury. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | nature | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1038/labinvest.2017.22 | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0023-6837 | |||||
書誌情報 |
en : Laboratory Investigation 巻 97, p. 833-842, 発行日 2017-07 |
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著者版フラグ | ||||||
値 | author | |||||
URI | ||||||
識別子 | http://doi.org/10.1038/labinvest.2017.22 | |||||
識別子タイプ | DOI | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2237/27027 | |||||
識別子タイプ | HDL |