{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:44:21Z","timestamp":1789897461740,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T00:00:00Z","timestamp":1357516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/Aims<\/jats:title><jats:p>Statins, which are inhibitors of 3\u2010hydroxy\u20103\u2010methylglutaryl coenzyme A reductase and inhibit endogenous cholesterol synthesis, possess pleiotropic activities, such as anti\u2010inflammatory, anti\u2010oxidative and antifibrotic effects. Here, we investigated whether statins ameliorate steatohepatitis using a high\u2010fat and high\u2010cholesterol (<jats:styled-content style=\"fixed-case\">HFHC<\/jats:styled-content>) diet\u2010induced rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight\u2010week\u2010old male Sprague\u2013Dawley rats were fed control chow or<jats:styled-content style=\"fixed-case\">HFHC<\/jats:styled-content>diet. Half of the<jats:styled-content style=\"fixed-case\">HFHC<\/jats:styled-content>diet\u2010fed rats were orally administered 2\u00a0mg\/kg\/day rosuvastatin for 12\u00a0weeks. Hepatic injury, steatosis, fibrosis and markers of lipid peroxidation\/oxidant stress were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As previously reported, HFHC diet induced steatohepatitis in rat livers with hypercholesterolaemia. Rosuvastatin decreased Oil Red O stained\u2010positive areas, liver\/body weight ratio, serum total cholesterol levels and hepatic free fatty acid contents in HFHC diet\u2010fed rats. Further study revealed that rosuvastatin significantly decreased hepatic<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>expression of tumour necrosis factor\u2010\u03b1 and interleukin\u20106, serum alanine aminotransferase levels and hepatic lobular inflammation grade. Hepatic fibrosis was also ameliorated by rosuvastatin with decreases in hepatic<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>expression of transforming growth factor\u2010\u03b2, connective tissue growth factor and type\u20101 procollagen. Similarly, hepatic Sirius red stained or \u03b1\u2010smooth muscle actin stained\u2010positive areas and expression of markers of lipid peroxidation\/oxidant stress [hepatic 8\u2010hydroxy\u2010oxyguanosine and hepatic 4\u2010hydroxy\u20102\u2010nonenal] were decreased. Interestingly, whereas the expression of carnitine palmitoyltransferase\u20101 and long\u2010chain acyl\u2010CoA dehydrogenase was not affected, that of catalase and acyl\u2010coA oxidase was restored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that rosuvastatin improved not only hepatic steatosis but also hepatic injury and fibrosis via improved peroxisomal \u03b2\u2010oxidation in this rat<jats:styled-content style=\"fixed-case\">HFHC<\/jats:styled-content>model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12033","type":"journal-article","created":{"date-parts":[[2012,11,3]],"date-time":"2012-11-03T15:36:11Z","timestamp":1351956971000},"page":"301-311","source":"Crossref","is-referenced-by-count":52,"title":["Rosuvastatin ameliorates high\u2010fat and high\u2010cholesterol diet\u2010induced nonalcoholic steatohepatitis in rats"],"prefix":"10.1111","volume":"33","author":[{"given":"Yoshihisa","family":"Okada","sequence":"first","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Medicine Saiseikai Kyoto Hospital Nagaoka\u2010kyo City Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichiro","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayasu","family":"Jo","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Mitsumoto","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Tochiki","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohichiroh","family":"Yasui","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Mitsuyoshi","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahito","family":"Minami","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Kagawa","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Okanoue","sequence":"additional","affiliation":[{"name":"Hepatology Center Saiseikai Suita Hospital Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Itoh","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0025-6196(24)00530-5","article-title":"Nonalcoholic steatohepatitis: Mayo Clinic experience with a hitherto unnamed disease","volume":"55","author":"Ludwig J","year":"1980","journal-title":"Mayo Clinic Proc"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50161"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-0349"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-143-10-200511150-00009"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.12.3541"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(01)01454-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1331\/1544345054475522"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.5.499"},{"key":"e_1_2_6_10_1","article-title":"Effects of lipid\u2010lowering therapy with strong statin on serum polyunsaturated fatty acid levels in patients with coronary artery disease","author":"Kurisu S","year":"2011","journal-title":"Heart Vessels"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.13.jpc60002"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0807646"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-009-0150-y"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000157145.98200.55"},{"key":"e_1_2_6_15_1","first-page":"997","article-title":"Rosuvastatin, a new HMG\u2010CoA reductase inhibitor, reduces the colonic inflammatory response in dextran sulfate sodium\u2010induced colitis in mice","volume":"17","author":"Naito Y","year":"2006","journal-title":"Int J Mol Med"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31804a5e34"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.11.016"},{"key":"e_1_2_6_18_1","first-page":"92","article-title":"Rosuvastatin reduces nonalcoholic fatty liver disease in patients with chronic hepatitis C treated with \u03b1\u2010interferon and ribavirin: rosuvastatin reduces NAFLD in HCV patients","volume":"11","author":"Malaguarnera M","year":"2011","journal-title":"Hepat Mon"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.6577"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704173"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014145"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl810"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060882"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32834abceb"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-88"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00299.2009"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.025"},{"key":"e_1_2_6_28_1","first-page":"14","article-title":"Effects of statins on liver fibrosis reversibility and activities of lysosomal exoglycosidases","volume":"3","author":"Knas M","year":"2007","journal-title":"J Clin Exp Hepatol"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21874"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.67.235"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25789"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5688(03)00004-7"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21655"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00415.2011"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-002-0916-0"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.02.013"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21248"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2005.08.021"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110373"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.4.1477"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.04.004"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25721"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.06.040"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-003-1093-x"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.630194"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803020200"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00008.2012"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000143319.73503.38"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP45319"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12033","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.12033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T05:39:58Z","timestamp":1745127598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.12033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,7]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["10.1111\/liv.12033"],"URL":"https:\/\/doi.org\/10.1111\/liv.12033","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,7]]}}}