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Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

Citation

Lean, QY and Eri, RD and Randall-Demllo, S and Sohal, SS and Stewart, N and Peterson, GM and Guven, N and Patel, RP, Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses, PLoS One, 10, (7) Article e0134259. ISSN 1932-6203 (2015) [Refereed Article]


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Copyright Statement

2015 Lean et al. Licenced under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1371/journal.pone.0134259

Abstract

Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis.

Item Details

Item Type:Refereed Article
Keywords:heparin, colitis, HPLC
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmaceutical Sciences
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Public Health (excl. Specific Population Health) not elsewhere classified
Author:Lean, QY (Miss Qi Lean)
Author:Eri, RD (Associate Professor Raj Eri)
Author:Randall-Demllo, S (Mr Sarron Randall-Demllo)
Author:Sohal, SS (Dr Sukhwinder Sohal)
Author:Stewart, N (Dr Niall Stewart)
Author:Peterson, GM (Professor Gregory Peterson)
Author:Guven, N (Dr Nuri Guven)
Author:Patel, RP (Dr Rahul Patel)
ID Code:102102
Year Published:2015
Web of Science® Times Cited:8
Deposited By:Pharmacy
Deposited On:2015-07-29
Last Modified:2017-12-14
Downloads:224 View Download Statistics

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