ArticleJournal of biochemical and molecular toxicology2021
Shc inhibitor idebenone ameliorates liver injury and fibrosis in dietary NASH in mice.
Article in Journal of biochemical and molecular toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Polymer-lipid hybrid nanoparticles incorporating green coffee extract: enhancing treatment for hepatic steatosis and fibrosis through metabolomic insights.RSC advances · 2025Article
- P46Shc Inhibits Mitochondrial ACAA2 Thiolase, Exacerbating Mitochondrial Injury and Inflammation in Aging Livers.The American journal of pathology · 2025Article
- Idebenone: Clinical Potential Beyond Neurological Diseases.Drug design, development and therapy · 2025Review
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- Cysteine sulfenylation contributes to liver fibrosis via the regulation of EphB2-mediated signaling.Cell death & disease · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Shc expression rises in human nonalcoholic steatohepatitis (NASH) livers, and Shc-deficient mice are protected from NASH-thus Shc inhibition could be a novel therapeutic strategy for NASH. Idebenone was recently identified as the first small-molecule Shc inhibitor drug. We tested idebenone in the fibrotic methionine-choline 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 and Shc expression in the liver; decreased serum alanine aminotransferase and 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.
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Registered trials
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