DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Ji-Hoon | ko |
dc.contributor.author | Seo, Kang-Sik | ko |
dc.contributor.author | Tadi, Surendar | ko |
dc.contributor.author | Ahn, Bong-Hyun | ko |
dc.contributor.author | Lee, Jung-Uee | ko |
dc.contributor.author | Heo, Jun-Young | ko |
dc.contributor.author | Han, Jeongsu | ko |
dc.contributor.author | Song, Myoung-Sub | ko |
dc.contributor.author | Kim, Soon-Ha | ko |
dc.contributor.author | Yim, Yong-Hyeon | ko |
dc.contributor.author | Choi, Hueng-Sik | ko |
dc.contributor.author | Shong, Minho | ko |
dc.contributor.author | Kweon, GiRyang | ko |
dc.date.accessioned | 2023-04-12T06:02:07Z | - |
dc.date.available | 2023-04-12T06:02:07Z | - |
dc.date.created | 2023-04-12 | - |
dc.date.created | 2023-04-12 | - |
dc.date.created | 2023-04-12 | - |
dc.date.issued | 2013-05 | - |
dc.identifier.citation | ANTIOXIDANTS & REDOX SIGNALING, v.18, no.14, pp.1713 - 1722 | - |
dc.identifier.issn | 1523-0864 | - |
dc.identifier.uri | http://hdl.handle.net/10203/306154 | - |
dc.description.abstract | Aims: Acetaminophen (APAP)-induced liver injury is mainly due to the excessive formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) through the formation of a reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), in both humans and rodents. Here, we show that the indole-derived synthetic compound has a protective effect against APAP-induced liver injury in C57Bl/6 mice model. Results: NecroX-7 decreased tert-butylhydroperoxide (t-BHP)-and APAP-induced cell death and ROS/RNS formation in HepG2 human hepatocarcinoma and primary mouse hepatocytes. In mice, NecroX-7 decreased APAP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and 3-nitrotyrosine (3-NT) formation, and also protected mice from APAP-induced liver injury and lethality by binding directly to NAPQI. The binding of NecroX-7 to NAPQI did not require any of cofactors or proteins. NecroX-7 could only scavenge NAPQI when hepatocellular GSH levels were very low. Innovation: NecroX-7 is an indole-derived potent antioxidant molecule, which can be bound to some types of radicals and especially NAPQI. It is well known that the NAPQI is a major intermediate of APAP, which causes necrosis of hepatocytes in rodents and humans. Thus, blocking NAPQI formation or eliminating NAPQI are novel strategies for the treatment or prevention of APAP-induced liver injury instead of GSH replenishment. Conclusion: Our data suggest that the indole-derivative, NecroX-7, directly binds to NAPQI when hepatic GSH levels are very low and the NAPQI-NecroX-7 complex is secreted to the blood from the liver. NecroX-7 shows more preventive and similar therapeutic effects against APAP-induced liver injury when compared to the effect of N-acetylcysteine in C57Bl/6 mice. Antioxid. Redox Signal. 18, 1713-1722. | - |
dc.language | English | - |
dc.publisher | MARY ANN LIEBERT, INC | - |
dc.title | An Indole Derivative Protects Against Acetaminophen-Induced Liver Injury by Directly Binding to N-Acetyl-p-Benzoquinone Imine in Mice | - |
dc.type | Article | - |
dc.identifier.wosid | 000317099700001 | - |
dc.identifier.scopusid | 2-s2.0-84875960765 | - |
dc.type.rims | ART | - |
dc.citation.volume | 18 | - |
dc.citation.issue | 14 | - |
dc.citation.beginningpage | 1713 | - |
dc.citation.endingpage | 1722 | - |
dc.citation.publicationname | ANTIOXIDANTS & REDOX SIGNALING | - |
dc.identifier.doi | 10.1089/ars.2012.4677 | - |
dc.contributor.localauthor | Shong, Minho | - |
dc.contributor.nonIdAuthor | Park, Ji-Hoon | - |
dc.contributor.nonIdAuthor | Seo, Kang-Sik | - |
dc.contributor.nonIdAuthor | Tadi, Surendar | - |
dc.contributor.nonIdAuthor | Ahn, Bong-Hyun | - |
dc.contributor.nonIdAuthor | Lee, Jung-Uee | - |
dc.contributor.nonIdAuthor | Heo, Jun-Young | - |
dc.contributor.nonIdAuthor | Han, Jeongsu | - |
dc.contributor.nonIdAuthor | Song, Myoung-Sub | - |
dc.contributor.nonIdAuthor | Kim, Soon-Ha | - |
dc.contributor.nonIdAuthor | Yim, Yong-Hyeon | - |
dc.contributor.nonIdAuthor | Choi, Hueng-Sik | - |
dc.contributor.nonIdAuthor | Kweon, GiRyang | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | REACTIVE OXYGEN | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | COVALENT BINDING | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | HEPATOTOXICITY | - |
dc.subject.keywordPlus | MELATONIN | - |
dc.subject.keywordPlus | TOXICITY | - |
dc.subject.keywordPlus | ACETYLCYSTEINE | - |
dc.subject.keywordPlus | GLUTATHIONE | - |
dc.subject.keywordPlus | METABOLITES | - |
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