Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox

Sobbe, A., Bridle, K.R., Jaskowski, L., de Guzman, C.E., Santrampurwala, N., Clouston, A.D., Campbell, C.M., Subramaniam, V.N., & Crawford, D.H.G. (2015) Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox. Journal of Gastroenterology and Hepatology (Australia), 30(3), pp. 638-645.

View at publisher


Background and Aim

  • Development of effective antifibrotic treatments that can be translated to clinical practice is an important challenge in contemporary hepatology. A recent report on β-thalassemia patients demonstrated that deferasirox treatment reversed or stabilized liver fibrosis independent of its iron-chelating properties. In this study, we investigated deferasirox in cell and animal models to better understand its potential antifibrotic effects.


  • The LX-2 stellate cell line was treated with 5 μM or 50 μM deferasirox (Exjade, Novartis Pharmaceuticals Australia, North Ryde, NSW, Australia) for up to 120 h. Three-week-old multidrug resistance 2 null (Mdr2–/–) mice received oral deferasirox or vehicle for 4 weeks (30 mg/kg/day). Cells and liver tissue were collected for assessment of fibrosis and fibrogenic gene expression.


  • In LX-2 cells treated with 50 μM deferasirox for 12 h, α1(I)procollagen expression was decreased by 25%, with maximal reductions (10-fold) seen following 24–120 h of treatment. Similarly, α-smooth muscle actin (αSMA) expression was significantly lower. Alterations in matrix remodeling genes, specifically decreased expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2, were observed. There was no significant difference in hepatic hydroxyproline content in Mdr2–/– mice following deferasirox administration (vehicle: 395 ± 27 μg/g vs deferasirox: 421 ± 33 μg/g). Similarly, no changes in the expression of fibrogenic genes were observed.


  • Despite reductions in α1(I)procollagen and αSMA expression and alterations in matrix degradation genes in LX-2 cells, deferasirox did not exhibit antifibrotic activity in Mdr2–/– mice. Given the positive outcomes seen in human trials, it may be appropriate to study deferasirox in other animal models of fibrosis and/or for a longer duration of therapy.

Impact and interest:

1 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 99755
Item Type: Journal Article
Refereed: Yes
Keywords: deferasirox; ACTA2 protein, human; actin; benzoic acid derivative; deferasirox; gelatinase A; iron chelating agent; procollagen; triazole derivative, animal cell; animal experiment; animal model; animal tissue; antifibrotic effect; Article; beta thalassemia; cell proliferation; cell viability; clinical practice; controlled study; drug effect; female; gene expression; human; iron chelation; iron storage, Actins; Administration, Oral; Animals; Benzoates; Cells, Cultured; Disease Models, Animal; Gene Expression; Hepatic Stellate Cells; Humans; Iron Chelating Agents; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinase 2; Mice; Mice, Transgenic; Procollagen; Triazoles
DOI: 10.1111/jgh.12720
ISSN: 1440-1746
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Deposited On: 12 Oct 2016 01:10
Last Modified: 14 Oct 2016 04:25

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page