title: Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Microbiology and Immunology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou Province, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
authors.forename: Mingliang
authors.initials: M
authors.lastname: Cheng
authors.forename: Baofang
authors.initials: B
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Nie
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001628:Beverages; D029798:Blueberry Plants / Q000737:chemistry*; D002251:Carbon Tetrachloride / Q000009:adverse effects; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D015870:Gene Expression; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000199:Actins; D002251:Carbon Tetrachloride; D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D008315:Malondialdehyde; D008668:Metallothionein; D013482:Superoxide Dismutase; C499780:dan-shao-hua-xian; C498862:Acta2 protein, rat
references.citation: J Biol Chem. 2009 Aug 7;284(32):21165-76
references.pmid: 19531480
references.citation: Hepatol Res. 2010 Apr;40(4):337-45
references.pmid: 20070402
references.citation: Hepatobiliary Pancreat Dis Int. 2004 Nov;3(4):558-63
references.pmid: 15567745
references.citation: J Hepatol. 2001 Aug;35(2):297-306
references.pmid: 11580156
references.citation: Gastroenterology. 2002 Feb;122(2):568-71
references.pmid: 11832470
references.citation: Crit Rev Toxicol. 2003;33(2):105-36
references.pmid: 12708612
references.citation: J Agric Food Chem. 2008 Sep 24;56(18):8418-26
references.pmid: 18759450
references.citation: J Biol Chem. 2000 Jan 28;275(4):2247-50
references.pmid: 10644669
references.citation: Mol Ther. 2004 Dec;10(6):1130-9
references.pmid: 15564144
references.citation: Free Radic Biol Med. 2004 Aug 1;37(3):339-49
references.pmid: 15223067
references.citation: Mol Aspects Med. 2000 Jun;21(3):49-98
references.pmid: 10978499
references.citation: Exp Biol Med (Maywood). 2006 Feb;231(2):138-44
references.pmid: 16446489
references.citation: J Biol Chem. 2000 Dec 15;275(50):38957-60
references.pmid: 11042194
references.citation: J Agric Food Chem. 2004 Jun 16;52(12):4026-37
references.pmid: 15186133
references.citation: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3207-15
references.pmid: 18579766
references.citation: Arch Toxicol. 2009 Jun;83(6):519-48
references.pmid: 19448996
references.citation: Zhonghua Yi Xue Za Zhi. 2010 Sep 21;90(35):2504-8
references.pmid: 21092482
references.citation: Dig Liver Dis. 2007 Sep;39(9):849-56
references.pmid: 17652039
references.citation: Hepatobiliary Pancreat Dis Int. 2010 Apr;9(2):164-8
references.pmid: 20382588
references.citation: Free Radic Res. 2010 Jun;44(6):605-13
references.pmid: 20380594
references.citation: J Am Coll Cardiol. 2006 Oct 17;48(8):1688-97
references.pmid: 17045908
references.citation: J Hepatol. 1995 Jun;22(6):696-9
references.pmid: 7560864
references.citation: Dig Dis Sci. 2007 Dec;52(12):3348-54
references.pmid: 17436097
references.citation: J AOAC Int. 2000 Jul-Aug;83(4):950-6
references.pmid: 10995120
references.citation: Exp Biol Med (Maywood). 2006 Oct;231(9):1459-67
references.pmid: 17018867
references.citation: Am J Gastroenterol. 2003 May;98(5):1142-9
references.pmid: 12809840
references.citation: World J Gastroenterol. 2005 Aug 28;11(32):4953-6
references.pmid: 16124044
references.citation: World J Gastroenterol. 2010 Jun 7;16(21):2657-63
references.pmid: 20518088
references.citation: Cell Mol Life Sci. 2002 Apr;59(4):627-47
references.pmid: 12022471
references.citation: Tohoku J Exp Med. 2002 Jan;196(1):9-22
references.pmid: 12498322
references.citation: J Pineal Res. 2004 Sep;37(2):78-84
references.pmid: 15298665
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3389-94
references.pmid: 15728360