Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats (original) (raw)

Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats

Loading

  1. I A Leclercq1,
  2. C Sempoux2,
  3. P Stärkel1,
  4. Y Horsmans1
  5. 1Gastroenterology Unit, Université Catholique de Louvain (UCL), Brussels, Belgium
  6. 2Pathology Unit, Université Catholique de Louvain (UCL), Brussels, Belgium
  7. Correspondence to:
    Professor I Leclercq
    Laboratoire de Gastroenterologie, Université Catholique de Louvain, GAEN 53/79, Avenue Mounier, 53, B-1200 Brussels, Belgium; isabelle.leclercq{at}gaen.ucl.ac.be

Abstract

Aim: Peroxisome proliferator activated receptor γ (PPARγ) agonists have been shown to prevent hepatic fibrosis in rodents. We evaluated the therapeutic antifibrotic potential of the PPARγ agonist pioglitazone on established hepatic fibrosis.

Methods: Repeated injections of carbon tetrachloride (CCl4), a choline deficient diet, or bile duct ligation (BDL) were used to induce hepatic fibrosis in rats. Pioglitazone treatment was introduced at various time points. Therapeutic efficacy was assessed by comparison of the severity of hepatic fibrosis in pioglitazone treated versus untreated fibrotic controls.

Results: When introduced after two weeks of CCl4, pioglitazone reduced hepatic fibrosis, OH proline content, hepatic mRNA expression of collagen type I, and profibrotic genes, as well as the number of activated α smooth muscle actin positive hepatic stellate cells, compared with rats receiving CCl4 only, with no significant change in necroinflammation. When pioglitazone treatment was initiated after five weeks of CCl4, no antifibrotic effect was observed. Similarly, pioglitazone was associated with a reduced severity of fibrosis induced by a choline deficient diet when introduced early, while delayed treatment with pioglitazone remained ineffective. In contrast, pioglitazone failed to interrupt progression of fibrosis due to BDL, irrespective of the timing of its administration.

Conclusion: In rats, the therapeutic antifibrotic efficacy of pioglitazone is limited and dependent on the type of injury, duration of disease, and/or the severity of fibrosis at the time of initiation of treatment.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

View Full Text

Linked Articles

Read the full text or download the PDF:

Log in using your username and password

Read the full text or download the PDF:

Log in using your username and password