title: Effect of resveratrol on experimental non-alcoholic steatohepatitis.
abstract: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are increasing clinical problems for which effective treatments are required. The polyphenol resveratrol prevents the development of fatty liver disease in a number of experimental studies. We hypothesized that it could revert steatohepatitis, including hepatic inflammation and fibrosis, in an experimental NASH model. To induce hepatic steatohepatitis, a 65% fat, 2% cholesterol and 0.5% cholate (HFC) diet was fed to rats for 1 or 16 weeks, prior to treatment. Subsequently, the diet was supplemented with resveratrol (approx. 100mg/rat/day) to three intervention groups; week 2-4, 2-7 or 17-22. Treated animals were sacrificed at the end of each intervention period with appropriate control and HFC diet controls. Blood and liver were harvested for analysis. When commenced early, resveratrol treatment partially mitigated transaminase elevations, hepatic enlargement and TNFα induced protein-3 protein expression, but generally resveratrol treatment had no effect on elevated hepatic triglyceride levels, histological steatohepatitis or fibrosis. We observed a slight reduction in Collagen1α1 mRNA expression and no reduction in the mRNA expression of other markers of fibrosis, inflammation or steatosis (TGFβ, TNFα, α2-MG, or SREBP-1c). Resveratrol metabolites were detected in serum, including trans-resveratrol-3-O-sulphate/trans-resveratrol-4'-O-sulphate (mean concentration 7.9 μg/ml). Contrary to the findings in experimental steatosis, resveratrol treatment had no consistent therapeutic effect in alleviating manifest experimental steatohepatitis.
authors: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Denmark. Electronic address: saraheeb@rm.dk.
authors: Sara
authors: S
authors: Heebøll
authors: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors: Karen Louise
authors: KL
authors: Thomsen
authors: Centre for Liver Disease Research, University of Queensland, Brisbane, Australia.
authors: Andrew
authors: A
authors: Clouston
authors: Department of Clinical Medicine, Aarhus University, Denmark; Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Denmark.
authors: Elias Immanuel
authors: EI
authors: Sundelin
authors: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Denmark.
authors: Yulia
authors: Y
authors: Radko
authors: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Denmark.
authors: Lars Porskjær
authors: LP
authors: Christensen
authors: Storr Liver Centre, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Australia.
authors: Mehdi
authors: M
authors: Ramezani-Moghadam
authors: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors: Martin
authors: M
authors: Kreutzfeldt
authors: Department of Clinical Medicine, Aarhus University, Denmark; Department of Endocrinology, Aarhus University Hospital, Denmark.
authors: Steen Bønløkke
authors: SB
authors: Pedersen
authors: Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Denmark.
authors: Niels
authors: N
authors: Jessen
authors: Storr Liver Centre, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Australia.
authors: Lionel
authors: L
authors: Hebbard
authors: Storr Liver Centre, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Australia.
authors: Jacob
authors: J
authors: George
authors: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
authors: Henning
authors: H
authors: Grønbæk
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D014280:Triglycerides; D000077185:Resveratrol
keywords: Anti-inflammatory; Anti-oxidant; Experimental NASH model; NAFLD; NASH; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Polyphenol; Rat; Resveratrol