title: Probucol ameliorates the development of nonalcoholic steatohepatitis in rats fed high-fat diets.
abstract: OBJECTIVE
  We sought to evaluate the effects of probucol on steatohepatitis and associated molecular mechanisms in a rat model of nonalcoholic steatohepatitis (NASH) induced by high-fat diet (HFD).
  
  
  METHODS
  Forty male rats weighing 100-120 g were randomly assigned to the following treatments (n = 10 for each treatment): standard diet + normal saline (NC group), standard diet + 500 mg/kg/day probucol (NP group), HFD + normal saline (HD group), and HFD + 500 mg/kg/day probucol (HP group). All animals received the above treatments for 15 weeks. Lipid metabolism and steatohepatitis were assessed. Systemic insulin resistance, oxidative stress status, serum tumor necrosis factor-alpha (TNF-α) and adiponectin levels, and gene expression were examined.
  
  
  RESULTS
  High-fat feeding resulted in macrovesicular steatosis, lobular inflammation, and hepatocellular ballooning degeneration in the liver, coupled with increased concentrations of serum aspartate aminotransferase and alanine aminotransferase. Probucol exposure attenuated the biochemical and histological changes comparable with NASH. Moreover, probucol treatment significantly prevented the elevations of serum total cholesterol, low-density lipoprotein, and high-density lipoprotein and the increase in the expression of numerous lipid metabolism-related genes in HFD-fed rats. There were increased insulin sensitivity and serum adiponectin levels and enhanced hepatic AMP-activated protein kinase phosphorylation in the HP group. Probucol lessened the HFD-induced elevation of serum TNF-α and hepatic malondialdehyde and reduced antioxidant enzymatic activities.
  
  
  CONCLUSIONS
  Probucol shows beneficial effects on HFD-induced steatohepatitis by improving insulin resistance and attenuating oxidative stress and systemic inflammation.
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. ycwr@sohu.com
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Xiao
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Hua-Mei
authors.initials: HM
authors.lastname: Zhou
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D004041:Dietary Fats / Q000009:adverse effects*; D005234:Fatty Liver / Q000139:chemically induced / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000924:Anticholesteremic Agents; D004041:Dietary Fats; D011341:Probucol