Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis

Edward A Ross,1 Madelyn H Miller,2 Allison Pacheco,2 Alicia R Willenberg,1 Justine T Tigno-Aranjuez,2 Kaitlyn E Crawford3 1Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA; 2Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences...

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Autores principales: Ross EA, Miller MH, Pacheco A, Willenberg AR, Tigno-Aranjuez JT, Crawford KE
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Lenguaje:EN
Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:a75edf4892a34fb3a0f97b17c79006ae2021-11-04T19:00:26ZIntrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis1178-7023https://doaj.org/article/a75edf4892a34fb3a0f97b17c79006ae2021-11-01T00:00:00Zhttps://www.dovepress.com/intrarectal-xyloglucan-administration-reduces-disease-severity-in-the--peer-reviewed-fulltext-article-CEGhttps://doaj.org/toc/1178-7023Edward A Ross,1 Madelyn H Miller,2 Allison Pacheco,2 Alicia R Willenberg,1 Justine T Tigno-Aranjuez,2 Kaitlyn E Crawford3 1Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA; 2Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA; 3Department of Materials Science and Engineering, College of Engineering and Computer Sciences, University of Central Florida, Orlando, FL, USACorrespondence: Edward A RossDepartment of Medicine, College of Medicine, University of Central Florida, 6850 Lake Nona Blvd, Orlando, FL, 32827, USAEmail Edward.ross@ucf.eduBackground: The pathophysiology of inflammatory bowel diseases remains poorly understood and treatment remains suboptimal for many patients. We hypothesize that the inflammatory milieu secondarily prolongs the injury and attenuates healing. We propose primary or adjuvant therapy with biocompatible adhesives to restore a barrier to protect submucosal structures, particularly stem cells.Methods: We used the well-described mouse dextran sodium sulfate (DSS) model of colitis resembling human ulcerative colitis to test the therapeutic efficacy of intrarectal administration of the tamarind plant-derived xyloglucan (TXG) polymer adhesive which underwent extensive analytic characterization. Mice in control, DSS-only, TXG-only, and DSS + TXG groups were studied for gross (weight, blood in stool, length of colon) and multiple histologic parameters.Results: Compared to DSS-only mice, TXG prevented the weight loss, occurrence of blood in the stool and colon shortening, with all those parameters not being statistically different from treatment naïve animals. Histologically, there was dramatic and highly statistically significant reduction in the total inflammatory index and protection from goblet cell loss, cellular infiltration, crypt abscess formation, epithelial erosion, granulation tissue, epithelial hyperplasia crypt irregularity and crypt loss. The TXG purity and characterization were established by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, and texture analysis.Conclusion: The striking attenuation of disease severity by intrarectal TXG use warrants future investigations of natural bioadhesives with well-established high safety profiles, and which could potentially be derivatized to include therapeutically active moieties for local drug delivery.Keywords: ulcerative colitis, dextran sodium sulfate, DSS, xyloglucan, tamarind, inflammatory bowel diseaseRoss EAMiller MHPacheco AWillenberg ARTigno-Aranjuez JTCrawford KEDove Medical Pressarticleulcerative colitisdextran sodium sulfatedssxyloglucantamarindinflammatory bowel diseaseDiseases of the digestive system. GastroenterologyRC799-869ENClinical and Experimental Gastroenterology, Vol Volume 14, Pp 429-439 (2021)
institution DOAJ
collection DOAJ
language EN
topic ulcerative colitis
dextran sodium sulfate
dss
xyloglucan
tamarind
inflammatory bowel disease
Diseases of the digestive system. Gastroenterology
RC799-869
spellingShingle ulcerative colitis
dextran sodium sulfate
dss
xyloglucan
tamarind
inflammatory bowel disease
Diseases of the digestive system. Gastroenterology
RC799-869
Ross EA
Miller MH
Pacheco A
Willenberg AR
Tigno-Aranjuez JT
Crawford KE
Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis
description Edward A Ross,1 Madelyn H Miller,2 Allison Pacheco,2 Alicia R Willenberg,1 Justine T Tigno-Aranjuez,2 Kaitlyn E Crawford3 1Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA; 2Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA; 3Department of Materials Science and Engineering, College of Engineering and Computer Sciences, University of Central Florida, Orlando, FL, USACorrespondence: Edward A RossDepartment of Medicine, College of Medicine, University of Central Florida, 6850 Lake Nona Blvd, Orlando, FL, 32827, USAEmail Edward.ross@ucf.eduBackground: The pathophysiology of inflammatory bowel diseases remains poorly understood and treatment remains suboptimal for many patients. We hypothesize that the inflammatory milieu secondarily prolongs the injury and attenuates healing. We propose primary or adjuvant therapy with biocompatible adhesives to restore a barrier to protect submucosal structures, particularly stem cells.Methods: We used the well-described mouse dextran sodium sulfate (DSS) model of colitis resembling human ulcerative colitis to test the therapeutic efficacy of intrarectal administration of the tamarind plant-derived xyloglucan (TXG) polymer adhesive which underwent extensive analytic characterization. Mice in control, DSS-only, TXG-only, and DSS + TXG groups were studied for gross (weight, blood in stool, length of colon) and multiple histologic parameters.Results: Compared to DSS-only mice, TXG prevented the weight loss, occurrence of blood in the stool and colon shortening, with all those parameters not being statistically different from treatment naïve animals. Histologically, there was dramatic and highly statistically significant reduction in the total inflammatory index and protection from goblet cell loss, cellular infiltration, crypt abscess formation, epithelial erosion, granulation tissue, epithelial hyperplasia crypt irregularity and crypt loss. The TXG purity and characterization were established by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, and texture analysis.Conclusion: The striking attenuation of disease severity by intrarectal TXG use warrants future investigations of natural bioadhesives with well-established high safety profiles, and which could potentially be derivatized to include therapeutically active moieties for local drug delivery.Keywords: ulcerative colitis, dextran sodium sulfate, DSS, xyloglucan, tamarind, inflammatory bowel disease
format article
author Ross EA
Miller MH
Pacheco A
Willenberg AR
Tigno-Aranjuez JT
Crawford KE
author_facet Ross EA
Miller MH
Pacheco A
Willenberg AR
Tigno-Aranjuez JT
Crawford KE
author_sort Ross EA
title Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis
title_short Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis
title_full Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis
title_fullStr Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis
title_full_unstemmed Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis
title_sort intrarectal xyloglucan administration reduces disease severity in the dextran sodium sulfate model of mouse colitis
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/a75edf4892a34fb3a0f97b17c79006ae
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