Comparative therapeutic effects of metformin and vitamin E in a model of non-alcoholic steatohepatitis in the young rat.
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.
Raso
Giuseppina Mattace
GM
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
Esposito
Emanuela
E
Iacono
Anna
A
Pacilio
Maria
M
Cuzzocrea
Salvatore
S
Canani
Roberto Berni
RB
Calignano
Antonio
A
Meli
Rosaria
R
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use*
D000975:Antioxidants; D014810:Vitamin E; D008687:Metformin