Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis

World J Gastroenterol. 2005 Aug 28;11(32):4931-8. doi: 10.3748/wjg.v11.i32.4931.


Aim: To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferator-activated receptor-gamma (PPAR-gamma), for liver tissue repair, and the development of ductular reaction, following common bile duct ligation (BDL) in rats.

Methods: Rats were supplemented with TGZ (0.2% w/w in the pelleted food) for 1 wk before BDL or sham operation. Animals were killed at 1, 2, or 4 wk after surgery.

Results: The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type I gene expression and liver hydroxy-proline levels. Accumulation of alpha-smooth-muscle actin (SMA)-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells (HSC) and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of gamma-glutamyl-transferase (GGT).

Conclusion: Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Ducts / drug effects
  • Bile Ducts / pathology*
  • Cell Division / drug effects
  • Cholestasis / drug therapy*
  • Cholestasis / pathology*
  • Chronic Disease
  • Disease Models, Animal
  • Hypoglycemic Agents / pharmacology*
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / pathology
  • Male
  • Rats
  • Rats, Wistar
  • Thiazolidinediones / pharmacology*


  • Hypoglycemic Agents
  • Thiazolidinediones
  • 2,4-thiazolidinedione