Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice

Ohkawara, Tatsuya; Okubo, Naoto; Maehara, Osamu; Nishihira, Jun; Takeda, Hiroshi

Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice

Ohkawara, Tatsuya; Okubo, Naoto; Maehara, Osamu et al.

Toxicology letters, 2021, 339, 51-59

Permalink : https://hdl.handle.net/2115/84553

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アクセス権	open access
URI	https://hdl.handle.net/2115/84553
タイトル	Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice
著者	Ohkawara, Tatsuya ; Okubo, Naoto ; Maehara, Osamu ; Nishihira, Jun ; Takeda, Hiroshi
e-Rad_Researcher 00374257 著者名 Ohkawara, Tatsuya
e-Rad_Researcher 00553207 著者名 Okubo, Naoto
e-Rad_Researcher 80836338 著者名 Maehara, Osamu
著者名 Nishihira, Jun
e-Rad_Researcher 60261294 著者名 Takeda, Hiroshi
言語	英語
キーワード	Acetaminophen
	ISO-1
	Macrophage migration inhibitory factor
	Liver injury
	RIPK3
発行日	2021-03-15
出版者	Elsevier
収録物名	Toxicology letters
巻(号)	339
ページ	51-59
抄録	Overdose use of acetaminophen (APAP) often occurs a severe liver injury, and its liver injury is lethal in some cases. Macrophage migration inhibitory factor (MIF) is expressed in a variety of cells and has multifunctional roles. However, the role of MIF in APAP-induced liver injury has not been fully investigated. In this study, we investigated whether treatment with (S,R)-3-(4-hydroxyphenil)-4,5dihydro-5-isoxazole acetic acid methyl ester (ISO-1), a MIF inhibitor, protected mice from acute APAP-induced liver injury. Acute liver injury was induced by injection of APAP (300 mg/kg body weight). Mice were treated with a single injection of ISO-1(15 mg/kg body weight) 1 h (h) before APAP administration. Histological, biochemical and molecular analyses were performed in liver of mice 12 h after APAP administration. ISO-1 remarkably improved the histological findings of APAP-induced liver injury in mice. The increases in serum levels of alanine aminotransferase (ALT), and macrophage inflammatory protein-2 (MIP-2) by APAP were inhibited by ISO-1. In addition, ISO-1 reduced the increased number of the myeloperoxidase-staining cells and that of TUNEL-positive staining cells in the liver of mice with APAP-induced liver injury. Up-regulation of hepatic receptor interacting protein kinase (RIPK)3 and heat shock protein70 by APAP was suppressed in the liver of mice given ISO-1. These results provide the additional evidence that inhibition of MIF activity may be clinically effective for treatment of acute APAP-induced liver injury. (C) 2020 Elsevier B.V. All rights reserved.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0378-4274
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.toxlet.2020.12.015