Document Detail


Comparative therapeutic effects of metformin and vitamin E in a model of non-alcoholic steatohepatitis in the young rat.
MedLine Citation:
PMID:  19135440     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Giuseppina Mattace Raso; Emanuela Esposito; Anna Iacono; Maria Pacilio; Salvatore Cuzzocrea; Roberto Berni Canani; Antonio Calignano; Rosaria Meli
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-14
Journal Detail:
Title:  European journal of pharmacology     Volume:  604     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-06-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  125-31     Citation Subset:  IM    
Affiliation:
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
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:
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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