Cited by 58Inflammatory Bowel DiseaseProteoglycans and glycosaminoglycans researchPolysaccharides Composition and Applications

Unfractionated heparin and new heparin analogues from ascidians (chordate-tunicate) ameliorate colitis in rats

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Belmiro, Celso L.R., Castelo-Branco, Morgana T.L., Melim, Leandra M.C., Schanaider, Alberto, Elia, Celeste, Madi, Kalil, Pavão, Mauro S.G., de Souza, Heitor S.P.·2009·Journal of Biological Chemistry

Abstract

The anti-inflammatory effect of mammalian heparin analogues, named dermatan sulfate and heparin, isolated from the ascidian Styela plicata was accessed in a TNBS-induced colitis model in rats. Subcutaneous administration of the invertebrate compounds during a 7-day period drastically reduced inflammation as observed by the normalization of the macroscopic and histological characteristics of the colon. At the molecular level, a decrease in the production of TNF-alpha, TGF-beta, and VEGF was observed, as well as a reduction of NF-kappaB and MAPK kinase activation. At the cellular level, the heparin analogues attenuated lymphocyte and macrophage recruitment and epithelial cell apoptosis. A drastic reduction in collagen-mediated fibrosis was also observed. No hemorrhagic events were observed after glycan treatment. These results strongly indicate the potential therapeutic use of these compounds for the treatment of colonic inflammation with a lower risk of hemorrhage when compared with mammalian heparin.

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Authors
Belmiro, C. L. R., Castelo-Branco, M. T. L., Melim, L. M. C., Schanaider, A., Elia, C., Madi, K., Pavão, M. S. G., & de Souza, H. S. P.
Affiliations
Universidade Federal do Rio de Janeiro (BR)
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-04
Volume
284
Issue
17
Pages
11267-11278
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1970693350
Cited by
57
References
64
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 4 · 2012: 2
FWCI
2.31
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Mizutani Foundation for Glycoscience
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Polysaccharides Composition and Applications
Keywords
unfractionated heparin, heparin analogues, dermatan sulfate, Styela plicata, colitis, TNBS-induced colitis, anti-inflammatory activity, NF-κB activation, MAPK signaling, TNF-α, TGF-beta, vascular endothelial growth factor, lymphocyte recruitment, macrophage recruitment, epithelial apoptosis, colonic fibrosis, bleeding risk
MeSH terms
Animals, Colitis, Collagen, Colon, Fibrosis, Hemorrhage, Heparin, Lymphocytes, Macrophages, Male, Models, Biological, Rats, Wistar, Apoptosis, Chordata, Rats

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