Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats

PLoS One. 2013;8(3):e58659. doi: 10.1371/journal.pone.0058659. Epub 2013 Mar 12.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Beverages*
  • Blueberry Plants / chemistry*
  • Carbon Tetrachloride / adverse effects
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Dietary Supplements*
  • Drugs, Chinese Herbal / administration & dosage
  • Gene Expression
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / metabolism*
  • Liver Cirrhosis, Experimental / prevention & control
  • Male
  • Malondialdehyde / metabolism
  • Metallothionein / genetics
  • Metallothionein / metabolism*
  • Rats
  • Superoxide Dismutase / metabolism
  • Up-Regulation


  • Actins
  • Collagen Type III
  • Drugs, Chinese Herbal
  • dan-shao-hua-xian
  • smooth muscle actin, rat
  • Malondialdehyde
  • Metallothionein
  • Carbon Tetrachloride
  • Superoxide Dismutase

Grant support

This study was supported by a grant from the Department of Science and Technology of Guizhou Province for Traditional Chinese Medicine Modernization (Grant No. ZY[2012]3017), a grant from the Foundation of the Governor of Guizhou Province ([2012] 44), and a grant from the National Foundation for Educational Teams of China ([2009]12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.