{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:55:29Z","timestamp":1761663329411},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,1,10]],"date-time":"2015-01-10T00:00:00Z","timestamp":1420848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Science, ICT & Future Planning","award":["2012R1A2A1A03002833"],"award-info":[{"award-number":["2012R1A2A1A03002833"]}]},{"name":"Korean Healthcare Technology R&D Project","award":["A100588"],"award-info":[{"award-number":["A100588"]}]},{"name":"Ministry of Education","award":["2013R1A1A2058889"],"award-info":[{"award-number":["2013R1A1A2058889"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Nonalcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>) is associated with cirrhosis and hepatocellular carcinoma. Reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) and reactive nitrogen species (<jats:styled-content style=\"fixed-case\">RNS<\/jats:styled-content>) play key roles in the development of the disease. However, the therapeutic target of <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> has not been fully defined and new treatments are needed. We investigated the protective effects of the antioxidant indole\u2010derived NecroX\u20107 in a <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> mouse model using leptin\u2010deficient <jats:italic>ob\/ob<\/jats:italic> and methionine\u2010 and choline\u2010deficient (<jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content>) diet\u2010fed <jats:italic>ob\/ob<\/jats:italic> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six\u2010week\u2010old male mice were divided into three groups: <jats:italic>ob\/+<\/jats:italic> mice, <jats:italic>ob\/ob<\/jats:italic> mice treated with vehicle and <jats:italic>ob\/ob<\/jats:italic> mice treated daily with NecroX\u20107 (20\u00a0mg\/kg) for 4\u00a0weeks. To study the effects of NecroX\u20107 in a fibrosis model, <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> was induced by feeding <jats:italic>ob\/ob<\/jats:italic> mice an <jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content> diet. The effects of NecroX\u20107 on <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> progression were evaluated using biochemical, histological and molecular markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NecroX\u20107\u2010treated <jats:italic>ob\/ob<\/jats:italic> mice had a marked decrease in serum aspartate aminotransferase and alanine transaminase compared with vehicle\u2010treated controls. Interestingly, hepatic steatosis and lipid peroxidation were significantly improved by NecroX\u20107 treatment. NecroX\u20107 inhibited <jats:italic>tert<\/jats:italic>\u2010butylhydroperoxide\u2010 and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced mitochondrial <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">RNS<\/jats:styled-content> in primary hepatocytes and attenuated mitochondrial dysfunction <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Furthermore, NecroX\u20107\u2010treated mice exhibited fewer infiltrating macrophages and reduced hepatic tumour necrosis factor\u2010alpha expression. Hepatic fibrosis in <jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content>\u2010fed <jats:italic>ob\/ob<\/jats:italic> mice was significantly decreased by NecroX\u20107 treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NecroX\u20107 treatment improved hepatic steatosis and fibrosis in murine <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> models. These effects occurred through the suppression of whole\u2010cell <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">RNS<\/jats:styled-content> and inflammatory responses and suggest that NecroX\u20107 has a potential therapeutic benefit in steatohepatitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12741","type":"journal-article","created":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T17:33:33Z","timestamp":1417455213000},"page":"1341-1353","source":"Crossref","is-referenced-by-count":30,"title":["The indole derivative NecroX\u20107 improves nonalcoholic steatohepatitis in <i>ob\/ob<\/i> mice through suppression of mitochondrial <scp>ROS<\/scp>\/<scp>RNS<\/scp> and inflammation"],"prefix":"10.1111","volume":"35","author":[{"given":"Hyo Kyun","family":"Chung","sequence":"first","affiliation":[{"name":"Research Center for Endocrine &amp; Metabolic Diseases Chungnam National University School of Medicine Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Center for Endocrine &amp; 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