Effect of resveratrol on experimental non-alcoholic steatohepatitis

Heebøll, Sara, Thomsen, Karen Louise, Clouston, Andrew, Sundelin, Elias Immanuel, Radko, Yulia, Christensen, Lars Porskjær, Ramezani-Moghadam, Mehdi, Kreutzfeldt, Martin, Pedersen, Steen Bønløkke, Jessen, Niels, George, Jacob, and Grønbæk, Henning (2015) Effect of resveratrol on experimental non-alcoholic steatohepatitis. Pharmacological research, 95-96. pp. 34-41.

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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. 100 mg/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.

Item ID: 40190
Item Type: Article (Research - C1)
ISSN: 1096-1186
Funders: Aarhus University, Danish Council for Independent Research (DCIR) - Medical Sciences, NOVO Nordisk Foundation, University of Sydney, National Health and Medical Research Council of Australia (NHMRC)., Cancer Council NSW (CC)
Projects and Grants: DCIR No. 11-107912, NHMRC Program Grant No. 1053206, NHMRC Project grant No. 632630, NHMRC Project grant No. 1049857, CC Project Grant 1069733
Date Deposited: 26 Aug 2015 01:36
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110104 Medical Biochemistry: Lipids @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 100%
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