{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:04:27Z","timestamp":1791194667382,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T00:00:00Z","timestamp":1327017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background and Aim:\u2002<\/jats:bold>Acetaminophen overdose is the most frequent cause of acute liver failure. Non\u2010alcoholic fatty liver disease is the most common chronic condition of the liver. The aim was to assess whether non\u2010alcoholic steatosis sensitizes rat liver to acute toxic effect of acetaminophen.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold>Male Sprague\u2013Dawley rats were fed a standard diet (ST\u20101, 10% kcal fat) and high\u2010fat gelled diet (HFGD, 71% kcal fat) for 6\u2003weeks and then acetaminophen was applied in a single dose (1\u2003g\/kg body weight). Animals were killed 24, 48 and 72\u2003h after acetaminophen administration. Serum biochemistry, activities of mitochondrial complexes, hepatic malondialdehyde, reduced and oxidized glutathione, triacylglycerol and cholesterol contents, and concentrations of serum and liver cytokines (TNF\u2010\u03b1, TGF\u2010\u03b21) were measured and histopathological samples were prepared.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold>The degree of liver inflammation and hepatocellular necrosis were significantly higher in HFGD fed animals after acetaminophen administration. Serum markers of liver injury were elevated only in acetaminophen treated HFGD fed animals. Concentration of hepatic reduced glutathione and ratio of reduced\/oxidized glutathione were decreased in both ST\u20101 and HFGD groups at 24\u2003h after acetaminophen application. Mild oxidative stress induced by acetaminophen was confirmed by measurement of malondialdehyde. Liver content of TNF\u2010\u03b1 was not significantly altered, but hepatic TGF\u2010\u03b21 was elevated in acetaminophen treated HFGD rats. We did not observe acetaminophen\u2010induced changes in activities of respiratory complexes I, II, and IV and activity of caspase\u20103.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold>Liver from rats fed HFGD is more susceptible to acute toxic effect of acetaminophen, compared to non\u2010steatotic liver.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2011.06807.x","type":"journal-article","created":{"date-parts":[[2011,6,7]],"date-time":"2011-06-07T13:17:41Z","timestamp":1307452661000},"page":"323-330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Susceptibility of rat non\u2010alcoholic fatty liver to the acute toxic effect of acetaminophen"],"prefix":"10.1111","volume":"27","author":[{"given":"Otto","family":"Ku\u010dera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Rou\u0161ar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavla","family":"Sta\u0148kov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Ha\u0148\u00e1\u010dkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halka","family":"Lotkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Podhola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"\u010cervinkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,20]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2000.02074.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-42641"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122010744"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.12.1499"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050043"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2010.520319"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2007.04962.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx0255976"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715760903513017"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1109058"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.23060"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.3058"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030285"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i38.4773"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080868"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.07.016"},{"key":"e_1_2_6_18_2","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0022-3565(25)32974-5","article-title":"Increased resistance of diabetic rats to acetaminophen\u2010induced hepatotoxicity","volume":"220","author":"Price VF","year":"1982","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.094326"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.015107"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00361.2009"},{"key":"e_1_2_6_22_2","article-title":"Is rat liver affected by non\u2010alcoholic steatosis more susceptible to the acute toxic effect of thioacetamide?","author":"Kucera O","year":"2011","journal-title":"Int. J. Exp. Pathol."},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/79.3.502"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2005.09.011"},{"key":"e_1_2_6_25_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.33549\/physiolres.930578","article-title":"Tert\u2010butyl hydroperoxide selectively inhibits mitochondrial respiratory\u2010chain enzymes in isolated rat hepatocytes","volume":"54","author":"Drahota Z","year":"2005","journal-title":"Physiol. Res."},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90326-2"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2006.11.028"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)00174-2"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706930"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-008X(02)00037-6"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_6_33_2","doi-asserted-by":"crossref","first-page":"317","DOI":"10.33549\/physiolres.932022","article-title":"The effect of rat strain, diet composition and feeding period on the development of a nutritional model of non\u2010alcoholic fatty liver disease in rats","volume":"60","author":"Kucera O","year":"2011","journal-title":"Physiol. Res."},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2008.05543.x"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.02.031"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/10739680500383423"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701584163"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300104"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20969"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300502"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.10.006"},{"key":"e_1_2_6_42_2","first-page":"283","article-title":"Transforming growth factor beta gene expression is transiently enhanced at a critical stage during liver regeneration after CCl4 treatment","volume":"69","author":"Armendariz\u2010Borunda J","year":"1993","journal-title":"Lab. Invest."},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.29132"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2007.09.001"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.3.489"},{"key":"e_1_2_6_46_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-3565(25)29666-5","article-title":"Acetaminophen\u2010induced hepatic necrosis. IV. Protective role of glutathione","volume":"187","author":"Mitchell JR","year":"1973","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.03.021"},{"key":"e_1_2_6_48_2","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.1016\/S0021-9258(19)67754-9","article-title":"Actaminophen toxicity results in site\u2010specific mitochondrial damage in isolated mouse hepatocytes","volume":"266","author":"Burcham PC","year":"1991","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1134\/S199075081003008X"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.09.015"},{"key":"e_1_2_6_51_2","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/S0022-3565(25)21309-X","article-title":"Protection of acetaminophen\u2010induced hepatocellular apoptosis and necrosis by cholesteryl hemisuccinate pretreatment","volume":"279","author":"Ray SD","year":"1996","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/67.2.322"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2009.07.003"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1440-1746.2011.06807.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1440-1746.2011.06807.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:47:50Z","timestamp":1741222070000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1440-1746.2011.06807.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,20]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,2]]}},"alternative-id":["10.1111\/j.1440-1746.2011.06807.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1440-1746.2011.06807.x","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,20]]},"assertion":[{"value":"2012-01-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}