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Idebenone was recently identified as the first small\u2010molecule Shc inhibitor drug. We tested idebenone in the fibrotic methionine\u2010choline deficient (MCD) diet and the metabolic fast food diet (FFD) mouse models of NASH. In the fibrotic MCD NASH model, idebenone reduced Shc expression and phosphorylation in peripheral blood mononuclear cells\u00a0and Shc expression in the liver; decreased serum alanine aminotransferase\u00a0and aspartate aminotransferase; and attenuated liver fibrosis as observed by quantitative polymerase chain reaction (qPCR) and hydroxyproline quantification. In the metabolic FFD model, idebenone administration improved insulin resistance, and reduced inflammation and fibrosis shown with qPCR, hydroxyproline measurement, and histology. Thus, idebenone ameliorates NASH in two mouse models. As an approved drug with a benign safety profile, Idebenone could be a reasonable human NASH therapy.<\/jats:p>","DOI":"10.1002\/jbt.22876","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T06:37:01Z","timestamp":1628491021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Shc inhibitor idebenone ameliorates liver injury and fibrosis in dietary NASH in mice"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8967-2783","authenticated-orcid":false,"given":"Joy X.","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences School of Veterinary Medicine Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey","family":"Tomilov","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences School of Veterinary Medicine Davis California 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