The treatment with antibody of TNF-alpha reduces the inflammation, necrosis and fibrosis in the non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet

Inflammation. 2008 Apr;31(2):91-8. doi: 10.1007/s10753-007-9053-z. Epub 2007 Dec 8.

Abstract

To assess the effects of anti-TNF-alpha antibody (infliximab) in experimental steatohepatitis induced by methionine- and choline-deficient (MCD) diet. The study included thirty rats. One group received normal rat food, and two groups received MCD diet. The treatment group received a single dose intra-peritoneal infliximab (4 mg/kg), at week 8. MCD diet increased levels of AST, ALT, TNF-alpha, TGF-beta(1), tissue and plasma MDA (p < 0.05 for each). Moreover, it led to steatosis, ballooning degeneration, inflammation, fibrosis and increased actin expression, histopathologically (p < 0.05 for each). In this experimental steatohepatitis anti-TNF-alpha antibody decreased the levels of AST, ALT, TGF-beta(1) and plasma and tissue MDA (p < 0.05 for each). Moreover, inflammation, necrosis, actin expression and fibrosis decreased in anti-TNF-alpha group compared to placebo group (p < 0.05 for each). This study indicates that anti-TNF-alpha antibody is effective on necrosis, inflammation and fibrosis in the experimental model of non-alcoholic steatohepatitis, induced by MCD diet.

MeSH terms

  • Actins / metabolism
  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology*
  • Aspartate Aminotransferases / blood
  • Choline Deficiency / complications
  • Choline Deficiency / drug therapy*
  • Choline Deficiency / pathology
  • Diet
  • Disease Models, Animal
  • Fatty Liver / etiology
  • Fatty Liver / pathology
  • Fatty Liver / prevention & control*
  • Hepatitis / etiology
  • Hepatitis / pathology
  • Hepatitis / prevention & control*
  • Infliximab
  • Injections, Intraperitoneal
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control*
  • Male
  • Malondialdehyde / metabolism
  • Methionine / deficiency*
  • Necrosis
  • Rats
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Actins
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Methionine
  • Infliximab
  • Aspartate Aminotransferases
  • Alanine Transaminase