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Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats

Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strat...

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Autores principales: Chang, Ting, Ho, Hsin-Ling, Hsu, Shao-Jung, Chang, Ching-Chih, Tsai, Ming-Hung, Huo, Teh-Ia, Huang, Hui-Chun, Lee, Fa-Yauh, Hou, Ming-Chih, Lee, Shou-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747388/
https://www.ncbi.nlm.nih.gov/pubmed/31454890
http://dx.doi.org/10.3390/ijms20174161
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author Chang, Ting
Ho, Hsin-Ling
Hsu, Shao-Jung
Chang, Ching-Chih
Tsai, Ming-Hung
Huo, Teh-Ia
Huang, Hui-Chun
Lee, Fa-Yauh
Hou, Ming-Chih
Lee, Shou-Dong
author_facet Chang, Ting
Ho, Hsin-Ling
Hsu, Shao-Jung
Chang, Ching-Chih
Tsai, Ming-Hung
Huo, Teh-Ia
Huang, Hui-Chun
Lee, Fa-Yauh
Hou, Ming-Chih
Lee, Shou-Dong
author_sort Chang, Ting
collection PubMed
description Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strategy. Indole-3-carbinol (C9H9NO, I3C) and 3,3′-diindolymethane (DIM), formed by the breakdown of glucosinolate glucobrassicin, are prevalent in cruciferous vegetables and have anti-angiogenesis properties. We aimed to evaluate their influences on portal hypertension, the severity of mesenteric angiogenesis, and portosystemic collaterals in cirrhosis. Sprague-Dawley rats with common bile duct ligation (CBDL)-induced liver cirrhosis or sham operation (surgical control) were randomly allocated to receive I3C (20 mg/kg/3 day), DIM (5 mg/kg/day) or vehicle for 28 days. The systemic and portal hemodynamics, severity of portosystemic shunting, mesenteric angiogenesis, and mesenteric proangiogenic factors protein expressions were evaluated. Compared to vehicle, both DIM and I3C significantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIM significantly down-regulated pErk, and I3C down-regulated NFκB, pIκBα protein expressions, and reduced portosystemic shunting degree. The cruciferous vegetable byproducts I3C and DIM not only exerted a portal hypotensive effect but also ameliorated abnormal angiogenesis and portosystemic collaterals in cirrhotic rats.
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spelling pubmed-67473882019-09-27 Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats Chang, Ting Ho, Hsin-Ling Hsu, Shao-Jung Chang, Ching-Chih Tsai, Ming-Hung Huo, Teh-Ia Huang, Hui-Chun Lee, Fa-Yauh Hou, Ming-Chih Lee, Shou-Dong Int J Mol Sci Article Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strategy. Indole-3-carbinol (C9H9NO, I3C) and 3,3′-diindolymethane (DIM), formed by the breakdown of glucosinolate glucobrassicin, are prevalent in cruciferous vegetables and have anti-angiogenesis properties. We aimed to evaluate their influences on portal hypertension, the severity of mesenteric angiogenesis, and portosystemic collaterals in cirrhosis. Sprague-Dawley rats with common bile duct ligation (CBDL)-induced liver cirrhosis or sham operation (surgical control) were randomly allocated to receive I3C (20 mg/kg/3 day), DIM (5 mg/kg/day) or vehicle for 28 days. The systemic and portal hemodynamics, severity of portosystemic shunting, mesenteric angiogenesis, and mesenteric proangiogenic factors protein expressions were evaluated. Compared to vehicle, both DIM and I3C significantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIM significantly down-regulated pErk, and I3C down-regulated NFκB, pIκBα protein expressions, and reduced portosystemic shunting degree. The cruciferous vegetable byproducts I3C and DIM not only exerted a portal hypotensive effect but also ameliorated abnormal angiogenesis and portosystemic collaterals in cirrhotic rats. MDPI 2019-08-26 /pmc/articles/PMC6747388/ /pubmed/31454890 http://dx.doi.org/10.3390/ijms20174161 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Ting
Ho, Hsin-Ling
Hsu, Shao-Jung
Chang, Ching-Chih
Tsai, Ming-Hung
Huo, Teh-Ia
Huang, Hui-Chun
Lee, Fa-Yauh
Hou, Ming-Chih
Lee, Shou-Dong
Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats
title Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats
title_full Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats
title_fullStr Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats
title_full_unstemmed Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats
title_short Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats
title_sort glucobrassicin metabolites ameliorate the development of portal hypertension and cirrhosis in bile duct-ligated rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747388/
https://www.ncbi.nlm.nih.gov/pubmed/31454890
http://dx.doi.org/10.3390/ijms20174161
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