{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:04:28Z","timestamp":1791194668752,"version":"4.1.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"14","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      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                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -acetyl-\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      -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.\n                      <jats:bold>\n                        <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                      <\/jats:bold>\n                      NecroX-7 decreased\n                      <jats:italic toggle=\"yes\">tert<\/jats:italic>\n                      -butylhydroperoxide (\n                      <jats:italic toggle=\"yes\">t<\/jats:italic>\n                      -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.\n                      <jats:bold>\n                        <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                      <\/jats:bold>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Our data suggest that the indole-derivative, NecroX-7, directly binds to NAPQI when hepatic GSH levels are very low and the NAPQI\u2013NecroX-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.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      18, 1713\u20131722.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2012.4677","type":"journal-article","created":{"date-parts":[[2012,11,2]],"date-time":"2012-11-02T12:30:27Z","timestamp":1351859427000},"page":"1713-1722","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["An Indole Derivative Protects Against Acetaminophen-Induced Liver Injury by Directly Binding to\n                    <i>N<\/i>\n                    -Acetyl-\n                    <i>p<\/i>\n                    -Benzoquinone Imine in Mice"],"prefix":"10.1177","volume":"18","author":[{"given":"Ji-Hoon","family":"Park","sequence":"first","affiliation":[{"name":"Chungnam National University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Sik","family":"Seo","sequence":"additional","affiliation":[{"name":"Chungnam National 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