Comparative therapeutic effects of metformin and vitamin E in a model of non-alcoholic steatohepatitis in the young rat.

Abstract

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
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 604 Issue 1-3 Pg. 125-31 (Feb 14 2009) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 19135440 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Vitamin E
• Metformin

Topics

• 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)