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Digestive diseases and sciences

Probucol ameliorates the development of nonalcoholic steatohepatitis in rats fed high-fat diets.


PMID 22878918

Abstract

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). Forty male rats weighing 100-120xa0g were randomly assigned to the following treatments (nxa0=xa010 for each treatment): standard dietxa0+xa0normal saline (NC group), standard dietxa0+xa0500xa0mg/kg/day probucol (NP group), HFDxa0+xa0normal saline (HD group), and HFDxa0+xa0500xa0mg/kg/day probucol (HP group). All animals received the above treatments for 15xa0weeks. 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. 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. Probucol shows beneficial effects on HFD-induced steatohepatitis by improving insulin resistance and attenuating oxidative stress and systemic inflammation.