Modified Citrus Pectin Stops Progression of Liver Fibrosis by Inhibiting galectin-3 and Inducing Apoptosis of Stellate Cells

Can J Physiol Pharmacol. 2016 May;94(5):554-62. doi: 10.1139/cjpp-2015-0284. Epub 2015 Dec 16.

Abstract

Modified citrus pectin (MCP) is a pH modified form of the dietary soluble citrus peel fiber known as pectin. The current study aims at testing its effect on liver fibrosis progression. Rats were injected with CCl4 (1 mL/kg, 40% v/v, i.p., twice a week for 8 weeks). Concurrently, MCP (400 or 1200 mg/kg) was administered daily in drinking water from the first week in groups I and II (prophylactic model) and in the beginning of week 5 in groups III and IV (therapeutic model). Liver function biomarkers (ATL, AST, and ALP), fibrosis markers (laminin and hyaluronic acid), and antioxidant biomarkers (reduced glutathione (GSH) and superoxide dismutase (SOD)) were measured. Stained liver sections were scored for fibrosis and necroinflammation. Additionally, expression of galectin-3 (Gal-3), α-smooth muscle actin (SMA), tissue inhibitor metalloproteinase (TIMP)-1, collagen (Col)1A1, caspase (Cas)-3, and apoptosis related factor (FAS) were assigned. Modified pectin late administration significantly (p < 0.05) decreased malondialdehyde (MDA), TIMP-1, Col1A1, α-SMA, and Gal-3 levels and increased levels of FAS, Cas-3, GSH, and SOD. It also decreased percentage of fibrosis and necroinflammation significantly (p < 0.05). It can be concluded that MCP can attenuate liver fibrosis through an antioxidant effect, inhibition of Gal-3 mediated hepatic stellate cells activation, and induction of apoptosis.

Keywords: antioxidant; antioxydants; apoptose; apoptosis; citrus pectin; fibrose; fibrosis; foie; galectin-3; galectine-3; liver; pectine d’agrumes.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / adverse effects
  • Antioxidants / chemistry
  • Antioxidants / therapeutic use
  • Apoptosis*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Carbon Tetrachloride
  • Citrus / chemistry*
  • Dietary Fiber / administration & dosage
  • Dietary Fiber / adverse effects
  • Dietary Fiber / therapeutic use*
  • Dietary Supplements / adverse effects
  • Disease Progression
  • Fruit / chemistry
  • Galectin 3 / antagonists & inhibitors*
  • Galectin 3 / metabolism
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology
  • Hot Temperature
  • Hydrogen-Ion Concentration
  • Lipid Peroxidation
  • Liver / metabolism
  • Liver / pathology
  • Liver / physiopathology
  • Liver Cirrhosis, Experimental / diet therapy
  • Liver Cirrhosis, Experimental / metabolism
  • Liver Cirrhosis, Experimental / physiopathology
  • Liver Cirrhosis, Experimental / prevention & control*
  • Male
  • Oxidative Stress
  • Pectins / administration & dosage
  • Pectins / adverse effects
  • Pectins / chemistry
  • Pectins / therapeutic use*
  • Rats, Sprague-Dawley
  • Solubility

Substances

  • Antioxidants
  • Biomarkers
  • Dietary Fiber
  • Galectin 3
  • Pectins
  • Carbon Tetrachloride