Modulatory effects of curcumin, silybin-phytosome and alpha-R-lipoic acid against thioacetamide-induced liver cirrhosis in rats

Chem Biol Interact. 2014 Jun 5;216:26-33. doi: 10.1016/j.cbi.2014.03.009. Epub 2014 Apr 3.

Abstract

Liver cirrhosis is the final consequence of a progressive fibrotic process characterized by excessive collagen deposition and destruction of the normal liver architecture. This study aimed to investigate the protective effects of curcumin, silybin-phytosome and alpha-R-lipoic acid against thioacetamide-induced cirrhosis. Male rats were allocated into five groups of which one group received saline and served as normal control. Animals from groups 2-5 were treated with thioacetamide administered intraperitoneally at a dose of 200 mg/kg 3 times per week for 7 weeks. Group 2 was left untreated while groups from 3 to 5 were given a daily oral dose of curcumin, silybin-phytosome or alpha-R-lipoic acid simultaneously with thioacetamide. Increases in hepatic levels of malondialdehyde (MDA) and protein carbonyls (Pr Co) associated with thioacetamide administration were partially blocked in those groups receiving supplements. Glutathione (GSH) depletion, collagen deposition, matrix metalloproteinase-2 (MMP-2) activity, transforming growth factor-β1 (TGF-β1) level as well as α-smooth muscle actin (α-SMA) and heat shock protein-47 (HSP-47) gene expressions were also decreased in response to supplements administration. Serological analysis of liver function and histopathological examination reinforced the results. In conclusion, the present study highlights the antioxidant and the antifibrotic potentials of these supplements against chronic liver diseases caused by ongoing hepatic damage.

Keywords: Alpha-R-lipoic acid; Curcumin; Liver cirrhosis; Oxidative stress; Silybin-phytosome; Thioacetamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Biomarkers
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Curcumin / therapeutic use*
  • Gene Expression Regulation
  • HSP47 Heat-Shock Proteins / genetics
  • HSP47 Heat-Shock Proteins / metabolism
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / pathology
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Silybin
  • Silymarin / analogs & derivatives*
  • Silymarin / therapeutic use
  • Thioacetamide / toxicity*
  • Thioctic Acid / therapeutic use*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • HSP47 Heat-Shock Proteins
  • Silymarin
  • Transforming Growth Factor beta1
  • silybin-phytosome
  • Thioacetamide
  • Silybin
  • Thioctic Acid
  • Matrix Metalloproteinase 2
  • Curcumin