1. Effect of resveratrol on experimental non-alcoholic steatohepatitis.
- Author
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Heebøll S, Thomsen KL, Clouston A, Sundelin EI, Radko Y, Christensen LP, Ramezani-Moghadam M, Kreutzfeldt M, Pedersen SB, Jessen N, Hebbard L, George J, and Grønbæk H
- Subjects
- Animals, Antioxidants administration & dosage, Antioxidants metabolism, Disease Models, Animal, Female, Liver metabolism, Liver pathology, Liver Function Tests, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Organ Size drug effects, Rats, Wistar, Resveratrol, Stilbenes administration & dosage, Stilbenes metabolism, Treatment Outcome, Triglycerides metabolism, Antioxidants therapeutic use, Liver drug effects, Non-alcoholic Fatty Liver Disease drug therapy, Stilbenes therapeutic use
- 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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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