{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:08:58Z","timestamp":1790791738180,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,6,21]],"date-time":"2013-06-21T00:00:00Z","timestamp":1371772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\n<jats:list>\n\n<jats:list-item><jats:p>The aim of the present study was to establish a progressive steatohepatitis mouse model because few reported animal models of non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>) show the progression from fatty liver to steatohepatitis.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p><jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content> mice were fed a high\u2010fat diet (<jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>) to develop obesity and were either administered carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>) eight times (0.05\u00a0mL\/kg, s.c., once, followed by 0.1\u00a0mL\/kg, s.c., seven times) or not. Serum parameters and hepatic histopathology were examined. In a separate experiment, <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> was administered subcutaneously from 0 to eight times to <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\u2010fed obese mice to investigate progressive changes. Markers of oxidative stress, inflammation and apoptosis, as well as histopathological changes in the liver, were analysed.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\u2010fed obese mice showed fatty liver but not steatohepatitis. In contrast, <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\u2010fed mice administered <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> eight times showed histopathological features of steatohepatitis (fatty liver, inflammation, hepatocellular ballooning and fibrosis) and increased serum alanine aminotransferase levels. However, the multiple administration of <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> to obese mice reduced the ratio of reduced glutathione to oxidized glutathione, superoxide dismutase activity and mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> copy number, leading to the development of chronic oxidative stress, increased numbers of apoptotic cells and increased levels of both tumour necrosis factor\u2010\u03b1 and transforming growth factor\u2010\u03b2 m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. The resulting inflammation led to increased hydroxyproline content in the liver and fibrosis.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The present study demonstrates that multiple administration of <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> to <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\u2010fed obese mice induces chronic oxidative stress that triggers inflammation and apoptosis and leads to the development of fibrosis in the liver, resulting in progression from fatty liver to steatohepatitis. This murine model will be useful in the research of hepatic disorders.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/1440-1681.12102","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T11:27:12Z","timestamp":1366716432000},"page":"422-430","source":"Crossref","is-referenced-by-count":85,"title":["A high\u2010fat diet and multiple administration of carbon tetrachloride induces liver injury and pathological features associated with non\u2010alcoholic steatohepatitis in mice"],"prefix":"10.1111","volume":"40","author":[{"given":"Norihiro","family":"Kubota","sequence":"first","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoichi","family":"Kado","sequence":"additional","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyoshi","family":"Kano","sequence":"additional","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norie","family":"Masuoka","sequence":"additional","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriko","family":"Nagata","sequence":"additional","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiyasu","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Yakult Central Institute for Microbiological Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50193"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20012"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2008.07.030"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2001.01083.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230624"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.191"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050953"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00199.2004"},{"key":"e_1_2_6_10_1","first-page":"171","article-title":"Pro\u2010oxidant\u2010mediated hepatic fibrosis and effects of antioxidant intervention in murine dietary steatohepatitis","volume":"24","author":"Phung N","year":"2009","journal-title":"Int. J. Mol. Med."},{"key":"e_1_2_6_11_1","first-page":"233","article-title":"Commonly used animal models of non\u2010alcoholic steatohepatitis","volume":"8","author":"Fan JG","year":"2009","journal-title":"Hepatobil. Pancreat. Dis. Int."},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2008.05543.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70599-2"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01357-3"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(70)90355-4"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/713611034"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.193"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2006.00465.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70506-8"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8814"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20877"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2007.00008.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3121"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760100300321"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcg.0000212608.59090.08"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1586\/egh.11.6"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00907-7"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1440-1681.12102","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.12102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T15:27:45Z","timestamp":1696260465000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.12102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,21]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1111\/1440-1681.12102"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.12102","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,21]]}}}