| Comparative therapeutic effects of metformin and vitamin E in a model of non-alcoholic steatohepatitis in the young rat. | |
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MedLine Citation:
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PMID: 19135440 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Only in the last few years has non-alcoholic steatohepatitis been recognized as an important and relatively common liver disease. To date, the therapeutic options are limited, vitamin E and metformin have been proposed for the treatment of this condition, although their mechanisms are not completely clarified as yet. The aim of this study was to investigate the anti-inflammatory and anti-oxidative mechanisms of these drugs in an experimental model of non-alcoholic steatohepatitis in the young rat. Male rats, just after weaning, were divided into four groups: a control group that received a standard diet; a high fat diet group; two high fat diet fed groups treated with vitamin E or metformin, respectively. After 4 weeks, we evaluated in the liver the modification of lipid peroxidation, assessed by malondialdehyde, TNF-alpha levels, S-nitrosylated protein, inducible nitric oxide sinthase (iNOS), and peroxisome proliferators-activated receptors (PPAR) expression and metalloproteinase activity. High fat diet increased malondialdehyde, nitrotyrosilated proteins, and TNF-alpha tissue content. Moreover, a decrease of PPAR-alpha and an increase of PPAR-gamma expression were observed. An increase of metalloproteinase activity was also shown. Among drug treatments, metformin reduced body weight gain and fat mass, metalloproteinase activity, and TNF-alpha tissue content, while it restored PPAR-alpha expression and downregulated PPAR-gamma expression. Vitamin E reduced the oxidative damage, protein nitrotyrosilation, and tissue TNF-alpha levels. Moreover a decrease of PPAR-gamma expression was also shown. These findings confirm the efficacy of both drugs as therapeutic tools in preventing the early onset of liver damage and non-alcoholic fatty liver disease progression. |
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Authors:
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Giuseppina Mattace Raso; Emanuela Esposito; Anna Iacono; Maria Pacilio; Salvatore Cuzzocrea; Roberto Berni Canani; Antonio Calignano; Rosaria Meli |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-12-14 |
Journal Detail:
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Title: European journal of pharmacology Volume: 604 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-06 Completed Date: 2009-06-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 125-31 Citation Subset: IM |
Affiliation:
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Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / administration & dosage, therapeutic use* Blotting, Western Body Weight / drug effects Disease Models, Animal Fatty Liver / drug therapy*, etiology Lipid Peroxidation / drug effects Liver / drug effects*, enzymology, metabolism Male Metformin / administration & dosage, therapeutic use* Rats Rats, Sprague-Dawley Vitamin E / administration & dosage, therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 1406-18-4/Vitamin E; 657-24-9/Metformin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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