ubiquinone and Choline-Deficiency

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.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Choline Deficiency; Diet; Disease Models, Animal; Fast Foods; Leukocytes, Mononuclear; Liver; Liver Cirrhosis; Male; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phosphorylation; Protective Agents; Shc Signaling Adaptor Proteins; Signal Transduction; Therapeutics; Ubiquinone

Topics: Alanine Transaminase; Alkaline Phosphatase; Ammonia; Animals; Aspartate Aminotransferases; Bilirubin; Biomarkers; Brain-Derived Neurotrophic Factor; Choline; Choline Deficiency; Diet; Dose-Response Relationship, Drug; gamma-Glutamyltransferase; Interleukin-6; Liver; Male; Methionine; Neuroprotective Agents; Nitric Oxide; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar; Serum Albumin; Ubiquinone