title: Preventive role of genistein in an experimental non-alcoholic steatohepatitis model.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the preventive role of genistein, a phytoestrogen with a wide variety of pharmacological effects, in an experimental non-alcoholic steatohepatitis (NASH) model.
  
  
  METHODS
  Thirty-six Sprague-Dawley rats were divided into three groups. Group 1 (control) received only a standard rat diet, group 2 (placebo) was given a high fat diet (HFD) plus 0.5 mL/day saline subcutaneously, and group 3 (genistein group) a HFD plus subcutaneous genistein injection at dose of 0.2 mg/kg/day for 6 weeks. All rats were killed after 6 weeks. Serum aminotransferases, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and plasma and liver malondialdehyde (MDA) levels were measured. Additionally, steatosis, ballooning degeneration and inflammation of the liver were examined histopathologically.
  
  
  RESULTS
  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.001 for each), plasma and liver tissue MDA and plasma TNF-alpha levels (P < 0.001, <0.001, <0.01, respectively) were found to be higher in the placebo group than in the control group. TGF-beta levels, however, were comparable in the placebo and control groups (P > 0.05). Histopathologically, steatosis, inflammatory cells per mm(2) and ballooning degeneration were significantly higher in the placebo group than in the control group (P < 0.001 for each). Nevertheless, AST and ALT (P < 0.05 for each), plasma and liver tissue MDA (P < 0.05 for each) and plasma TNF-alpha levels (P < 0.001) were significantly decreased in the genistein group compared to the placebo group. Histopathologically, steatosis (P < 0.05), inflammatory cells per mm(2) and ballooning degeneration (P < 0.01 for each) in the genistein group were also significantly lower than in the placebo group.
  
  
  CONCLUSIONS
  Genistein, a strong antioxidant agent, significantly decreased the plasma TNF-alpha level and remarkably prevented the emergence of NASH by improving the biochemical and histopathological abnormalities via attenuating oxidative stress.
authors.affiliation: Division of Gastroenterology, Firat University School of Medicine, Elazig, Turkey. mehmetyalniz@hotmail.com
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yalniz
authors.forename: Ibrahim Halil
authors.initials: IH
authors.lastname: Bahcecioglu
authors.forename: Nalan
authors.initials: N
authors.lastname: Kuzu
authors.forename: Orhan Kursat
authors.initials: OK
authors.lastname: Poyrazoglu
authors.forename: Ozgur
authors.initials: O
authors.lastname: Bulmus
authors.forename: Selman
authors.initials: S
authors.lastname: Celebi
authors.forename: Bilal
authors.initials: B
authors.lastname: Ustundag
authors.forename: Ibrahim Hanefi
authors.initials: IH
authors.lastname: Ozercan
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D004041:Dietary Fats; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D006505:Hepatitis / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004041:Dietary Fats; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D019833:Genistein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase