Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats
Open accessAbstract
AIM: Peroxisome proliferator activated receptor gamma (PPARgamma) agonists have been shown to prevent hepatic fibrosis in rodents. We evaluated the therapeutic antifibrotic potential of the PPARgamma 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 alpha 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.
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The same PPARγ agonist failed to achieve beneficial results in a bile duct ligation model.
“In contrast to these findings, the same PPARγ agonist failed to achieve beneficial results in a bile duct ligation model.[138].”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [138]
Pioglitazone reduces hepatic fibrosis in a CCl4 and choline deficient diet model.
“the PPAR-γ agonist Pioglitazone was even shown to reduce hepatic fibrosis in a CCl 4 and choline deficient diet model and decrease pro-fibrotic gene expression (e.g., col1α1, αSma).[138]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [138]
Pioglitazone decreases pro-fibrotic gene expression such as col1α1 and αSma in that model.
“the PPAR-γ agonist Pioglitazone was even shown to reduce hepatic fibrosis in a CCl 4 and choline deficient diet model and decrease pro-fibrotic gene expression (e.g., col1α1, αSma).[138]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [138]
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- Authors
- Leclercq, I. A.
- Affiliations
- UCLouvain (BE)
- Corresponding author
- Leclercq, I A
- ORCID
- Leclercq, I A
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2006-02-16
- Volume
- 55
- Issue
- 7
- Pages
- 1020-1029
- ISSN
- 0017-5749 (ISSN-L)
- PMC
- PMC1856308
- OpenAlex
- W2121396535
- Cited by
- 67
- References
- 53
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 4 · 2022: 5 · 2021: 1 · 2020: 7 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 3 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- pioglitazone, liver fibrosis, PPARγ agonists, antifibrotic therapy, treatment timing, carbon tetrachloride, choline-deficient diet, bile duct ligation, hepatic stellate cells, type I collagen, hydroxyproline, therapeutic window
- MeSH terms
- Pioglitazone, Animals, Bile Ducts, Carbon Tetrachloride, Choline, Hypoglycemic Agents, Ligation, Liver Cirrhosis, Experimental, Male, RNA, Messenger, Time Factors, Treatment Outcome, Rats, Sprague-Dawley, Disease Progression, Collagen Type I, Thiazolidinediones, Rats
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