Dietary Supplementation of Blueberry Juice Enhances Hepatic Expression of Metallothionein and Attenuates Liver Fibrosis in Rats

Aim To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense. Methods Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques. Results Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver. Conclusion Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-03-12

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1371/journal.pone.0058659PMID 23554912PMCID 3595269
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Effects of blueberry on hepatic fibrosis and transcription factor Nrf2 in rats.

  2010cited by this paper
• [Effects of blueberry on the proliferation and activation of hepatic stellate cell and its mechanism].

  2010cited by this paper
• Protective effect of metallothionein on oxidative stress-induced DNA damage

  2010cited by this paper
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  2010cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2008cited by this paper
• Selective degeneration of central photoreceptors after hyperbaric oxygen in normal and metallothionein-knockout mice.

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  2006cited by this paper
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  2005cited by this paper
• Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma.

  2005cited by this paper
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  2004cited by this paper
• HIV-1 Tat-mediated protein transduction of Cu,Zn-superoxide dismutase into pancreatic beta cells in vitro and in vivo.

  2004cited by this paper
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  2004cited by this paper
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  2004cited by this paper
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  2004cited by this paper
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  2003cited by this paper
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  2003cited by this paper
• Metallothionein: the multipurpose protein

  2002cited by this paper
• Recent studies on metallothionein: protection against toxicity of heavy metals and oxygen free radicals.

  2002influential reference
• Hepatitis C virus proteins: direct link to hepatic oxidative stress, steatosis, carcinogenesis and more.

  2002cited by this paper
• Oxidative stress-related molecules and liver fibrosis.

  2001cited by this paper
• The Effects of Metallothionein on the Activity of Enzymes Involved in Removal of Reactive Oxygen Species

  2001cited by this paper
• Analysis of botanicals and dietary supplements for antioxidant capacity: a review.

  2000cited by this paper
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  2000cited by this paper
• Hepatic content of collagens and laminin in rat model of experimental liver fibrosis

  2000cited by this paper
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  2000cited by this paper
• Molecular Regulation of Hepatic Fibrosis, an Integrated Cellular Response to Tissue Injury*

  2000cited by this paper
• Pathogenesis of liver fibrosis: role of oxidative stress.

  2000cited by this paper
• Histological grading and staging of chronic hepatitis.

  1995cited by this paper
• Histological grading and staging of chronic hepatitis.

  1995cited by this paper
• Experimental Biology and Medicine Minireview Metallothionein and Liver Cell Regeneration

  year unknowncited by this paper

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