Antifibrotic activity of anthocyanidin delphinidin in carbon tetrachloride-induced hepatotoxicity in mice

Toxicology. 2010 Jun 4;272(1-3):1-10. doi: 10.1016/j.tox.2010.03.016. Epub 2010 Apr 3.


The aim of this study was to investigate the hepatoprotective effects of anthocyanidin delphinidin in carbon tetrachloride (CCl(4))-induced liver fibrosis in mice. Male Balb/C mice were treated with CCl(4) dissolved in olive oil (20%, v/v, 2mL/kg) intraperitoneally (i.p.), twice a week for 7 weeks. Delphinidin was administered i.p. once daily for next 2 weeks, in doses of 10 and 25mg/kg of body weight. The CCl(4) control group has been observed for spontaneous reversion of fibrosis. CCl(4)-administration induced an elevation in serum transaminase and alkaline phosphatase levels and increased oxidative stress in the liver. Delphinidin has successfully attenuated oxidative stress, increased matrix metalloproteinase-9 and metallothionein I/II expression and restored hepatic architecture. Furthermore, the overexpression of tumor necrosis factor-alpha and transforming growth factor-beta1 has been withdrawn by delphinidin. Concomitantly, the expression of alpha-smooth muscle actin indicated returning of hepatic stellate cells (HSC) into inactive state. Our results suggest the therapeutic effects of delphinidin in CCl(4)-induced liver fibrosis by promoting extracellular matrix degradation, HSC inactivation and down-regulation of fibrogenic stimuli, with strong enhancement of hepatic regenerative capability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthocyanins / pharmacology*
  • Carbon Tetrachloride / adverse effects*
  • Carbon Tetrachloride Poisoning / drug therapy*
  • Down-Regulation / drug effects
  • Drug-Related Side Effects and Adverse Reactions / drug therapy
  • Fibrosis / drug therapy
  • Fibrosis / pathology
  • Hepatic Stellate Cells / drug effects*
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / pathology
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Metallothionein / genetics
  • Mice
  • Mice, Inbred BALB C
  • Olive Oil
  • Plant Oils / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Tumor Necrosis Factor-alpha / genetics


  • Anthocyanins
  • Olive Oil
  • Plant Oils
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Metallothionein
  • Carbon Tetrachloride
  • Matrix Metalloproteinase 9
  • delphinidin