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Probucol Ameliorates the Development of Nonalcoholic Steatohepatitis in Rats Fed High-Fat Diets

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Abstract

Aims

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.

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Acknowledgments

This work was supported by the Natural Science Foundation of Chongqing of China (CSTC, 2010BB5105).

Conflict of interest

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Rong Wu, Wei Zhang, Bo Liu, Feng Zhang, Hua-mei Zhou, Xiao-ling Wu & Xia Zhang

  2. Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Jing Gao

  3. Institute of Life Sciences, Chongqing Medical University, Chongqing, China

    Xiao-qiu Xiao

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  1. Rong Wu
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  2. Wei Zhang
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Correspondence to Xiao-ling Wu or Xia Zhang.

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Wu, R., Zhang, W., Liu, B. et al. Probucol Ameliorates the Development of Nonalcoholic Steatohepatitis in Rats Fed High-Fat Diets. Dig Dis Sci 58, 163–171 (2013). https://doi.org/10.1007/s10620-012-2335-9

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