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Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats

BACKGROUND: Polyethylene glycosylated (PEGylated) porcine glucagon-like peptide-2 (pGLP-2) considerably increases half-life and stability compared with the native pGLP-2, but the effective dose for intestinal damage is still unclear. This study aims to evaluate the available dose of polyethylene gly...

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Autores principales: Qi, Ke-ke, Lv, Jia-jia, Wu, Jie, Xu, Zi-wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336612/
https://www.ncbi.nlm.nih.gov/pubmed/28259136
http://dx.doi.org/10.1186/s12876-017-0593-x
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author Qi, Ke-ke
Lv, Jia-jia
Wu, Jie
Xu, Zi-wei
author_facet Qi, Ke-ke
Lv, Jia-jia
Wu, Jie
Xu, Zi-wei
author_sort Qi, Ke-ke
collection PubMed
description BACKGROUND: Polyethylene glycosylated (PEGylated) porcine glucagon-like peptide-2 (pGLP-2) considerably increases half-life and stability compared with the native pGLP-2, but the effective dose for intestinal damage is still unclear. This study aims to evaluate the available dose of polyethylene glycosylated porcine glucagon-like peptide-2 (PEG-pGLP-2), a modified, long-acting form of pGLP-2 in an experimental rat model of ulcerative colitis. METHODS: Thirty-five male rats were randomly assigned into five groups: control, dextran sodium sulphate (DSS), DSS + PEG–pGLP-2(L), DSS + PEG–pGLP-2(M) and DSS + PEG–pGLP-2(H). Rats in control group received only water; other rats were fed with 5% (w/v) DSS and intraperitoneally administered with 12.5, 25 and 100 nmol/kg PEG–pGLP-2 daily for 6 days. RESULTS: Compared with the control treatment, DSS treatment significantly (p < 0.05) decreased body weight change, colonic length, duodenal villus height and expression of zonula occludens-1, whereas significantly (p < 0.05) increased colonic damage score and expression of claudin-1, interleukin (IL)-1, IL-7, IL-10, interferon-γ and tumour necrosis factor (TNF)-α in colon. However, the three doses of PEG–pGLP-2 all reduced these effects; these treatments significantly (p < 0.05) increased body weight change and duodenal villus height, whereas significantly (p < 0.05) decreased colonic damage score and expression of IL-1, IL-7 and TNF-α in colon. Specifically, low-dose (12.5 nmol/kg/d) PEG–pGLP-2 was effective. CONCLUSIONS: These results indicated that PEG–pGLP-2 is a novel and potentially effective therapy for intestinal healing in a relatively low dose. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12876-017-0593-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-53366122017-03-07 Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats Qi, Ke-ke Lv, Jia-jia Wu, Jie Xu, Zi-wei BMC Gastroenterol Research Article BACKGROUND: Polyethylene glycosylated (PEGylated) porcine glucagon-like peptide-2 (pGLP-2) considerably increases half-life and stability compared with the native pGLP-2, but the effective dose for intestinal damage is still unclear. This study aims to evaluate the available dose of polyethylene glycosylated porcine glucagon-like peptide-2 (PEG-pGLP-2), a modified, long-acting form of pGLP-2 in an experimental rat model of ulcerative colitis. METHODS: Thirty-five male rats were randomly assigned into five groups: control, dextran sodium sulphate (DSS), DSS + PEG–pGLP-2(L), DSS + PEG–pGLP-2(M) and DSS + PEG–pGLP-2(H). Rats in control group received only water; other rats were fed with 5% (w/v) DSS and intraperitoneally administered with 12.5, 25 and 100 nmol/kg PEG–pGLP-2 daily for 6 days. RESULTS: Compared with the control treatment, DSS treatment significantly (p < 0.05) decreased body weight change, colonic length, duodenal villus height and expression of zonula occludens-1, whereas significantly (p < 0.05) increased colonic damage score and expression of claudin-1, interleukin (IL)-1, IL-7, IL-10, interferon-γ and tumour necrosis factor (TNF)-α in colon. However, the three doses of PEG–pGLP-2 all reduced these effects; these treatments significantly (p < 0.05) increased body weight change and duodenal villus height, whereas significantly (p < 0.05) decreased colonic damage score and expression of IL-1, IL-7 and TNF-α in colon. Specifically, low-dose (12.5 nmol/kg/d) PEG–pGLP-2 was effective. CONCLUSIONS: These results indicated that PEG–pGLP-2 is a novel and potentially effective therapy for intestinal healing in a relatively low dose. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12876-017-0593-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-04 /pmc/articles/PMC5336612/ /pubmed/28259136 http://dx.doi.org/10.1186/s12876-017-0593-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Qi, Ke-ke
Lv, Jia-jia
Wu, Jie
Xu, Zi-wei
Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats
title Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats
title_full Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats
title_fullStr Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats
title_full_unstemmed Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats
title_short Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats
title_sort therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336612/
https://www.ncbi.nlm.nih.gov/pubmed/28259136
http://dx.doi.org/10.1186/s12876-017-0593-x
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