{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:10:22Z","timestamp":1771261822917,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T00:00:00Z","timestamp":1384214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Non\u2010alcoholic steatohepatitis (NASH) is a progressive form of non\u2010alcoholic fatty liver disease (NAFLD) and is a major cause of liver cirrhosis and hepatic failure. The methionine choline\u2010deficient diet (MCD) is a frequently used hepatotoxicity animal model of NASH that induces hepatic transaminase (ALT, AST) elevations and hepatobiliary histological changes similar to those observed in human NASH. Liver\u2010specific microRNA\u2010122 (miR\u2010122) has been shown as a key regulator of cholesterol and fatty acid metabolism in adult liver, and has recently been proposed as a sensitive and specific circulating biomarker of hepatic injury. The purpose of this study was to assess miR\u2010122 serum levels in mice receiving an MCD diet for 0, 3, 7, 14, 28 and 56 days and compare the performance vs. routine clinical chemistry when benchmarked against the histopathological liver findings. MiR\u2010122 levels were quantified in serum using RT\u2010qPCR. Both miR\u2010122 and ALT\/AST levels were significantly elevated in serum at all timepoints. MiR\u2010122 levels increased on average by 40\u2010fold after 3 days of initiating the MCD diet, whereas ALT and AST changes were 4.8\u2010 and 3.3\u2010fold, respectively. In general, miR\u2010122 levels remained elevated across all time points, whereas the ALT\/AST increases were less robust but correlated with the progressive severity of NASH as assessed by histopathology. In conclusion, serum levels of miR\u2010122 can potentially be used as a sensitive biomarker for the early detection of hepatotoxicity and can aid in monitoring the extent of NAFLD\u2010associated liver injury in mouse efficacy models. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.2960","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T01:38:50Z","timestamp":1384220330000},"page":"726-732","source":"Crossref","is-referenced-by-count":40,"title":["Circulating microRNA 122 in the methionine and choline\u2010deficient mouse model of non\u2010alcoholic steatohepatitis"],"prefix":"10.1002","volume":"34","author":[{"given":"John D.","family":"Clarke","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Arizona  Tucson AZ 85721 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Sharapova","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago IL 60064 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"April D.","family":"Lake","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Arizona  Tucson AZ 85721 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Blomme","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago IL 60064 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Maher","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago IL 60064 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan J.","family":"Cherrington","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Arizona  Tucson AZ 85721 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890802552437"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2011.577740"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2006.00465.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019055108"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.161"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023937"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25762"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.1.2.1066"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22569"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.211"},{"key":"e_1_2_8_12_1","first-page":"1428","article-title":"Circulating microRNA\u2010122 as a potential biomarker for liver injury","volume":"5","author":"Ding X","year":"2012","journal-title":"Mol. 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