Ameliorative potential of omega 3 fatty acids and HMG-CoA reductase inhibitors on experimentally-induced non-alcoholic steatohepatitis

Prostaglandins Leukot Essent Fatty Acids. 2015 May:96:1-9. doi: 10.1016/j.plefa.2014.12.003. Epub 2014 Dec 13.

Abstract

Non-alcoholic steatohepatitis (NASH) has a relation to obesity. It may lead to hepatocellular carcinoma. To date, the therapeutic options are limited due to complex pathogenesis. This study aimed to investigate the effect of atorvastatin and omega 3 fatty acids on experimentally-induced NASH. Sixty male albino rats were divided into 6 equal groups; control group, high fat emulsion/sucrose (HFE/S) diet, HFE/S+carboxymethyl cellulose, HFE/S +Atorvastatin, HFE/S+Fish oil and HFE/S+Atorvastatin+Fish oil. Serum alanine aminotransferase, total cholesterol (TC), triglycerides (TG), high density lipoproteins, insulin, glucose, C-reactive protein and quantitative insulin sensitivity check index were measured. Also, hepatic TC, TG, malondialdehyde, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor beta 1 (TGF-β1) were determined. Liver sections were examined histopathologically. Atorvastatin improved lipid profile, inflammation and oxidative stress but did not improve insulin resistance, hepatic TGF-β1 or body weight while fish oil improved lipid profile, decreased inflammation and oxidative stress, improved insulin resistance, hepatic TGF-β1 and body weight compared to HFE/S group. Atorvastatin/fish oil combination produced significant improvement in the lipid profile, inflammation, oxidative stress, insulin resistance, hepatic TGF-β1 and body weight compared to the use of each of these drugs alone. This might be attributed to the effect of fish oil on the lipid profile, inflammatory cytokines, insulin resistance and TGF-β1 which potentiates the effect of atorvastatin on NASH.

Keywords: Atorvastatin; Cholesterol; Fish oil; NASH.

MeSH terms

  • Animals
  • Atorvastatin / metabolism
  • Atorvastatin / therapeutic use*
  • Body Weight / drug effects
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-3 / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation / metabolism
  • Insulin Resistance
  • Lipids / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Rats, Wistar
  • Sucrose / adverse effects
  • Sucrose / blood

Substances

  • Cytokines
  • Fatty Acids, Omega-3
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Sucrose
  • Atorvastatin