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Open AccessArticle

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

1
Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
2
Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan
3
Division of Gastroenterology and Hepatology, Department of Medicine, Lotong Poh-Ai Hospital, Yilan 26546, Taiwan
4
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan
5
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
6
Chang Gung University College of Medicine and Division of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
7
Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan
8
Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei 11217, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(17), 4161; https://doi.org/10.3390/ijms20174161
Received: 27 June 2019 / Revised: 11 August 2019 / Accepted: 24 August 2019 / Published: 26 August 2019
(This article belongs to the Special Issue Liver Damage and Repair)
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. View Full-Text
Keywords: indole-3-carbinol (I3C); 3,3′-diindolymethane (DIM); liver cirrhosis; portosystemic collaterals; angiogenesis indole-3-carbinol (I3C); 3,3′-diindolymethane (DIM); liver cirrhosis; portosystemic collaterals; angiogenesis
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MDPI and ACS Style

Chang, T.; Ho, H.-L.; Hsu, S.-J.; Chang, C.-C.; Tsai, M.-H.; Huo, T.-I.; Huang, H.-C.; Lee, F.-Y.; Hou, M.-C.; Lee, S.-D. Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats. Int. J. Mol. Sci. 2019, 20, 4161. https://doi.org/10.3390/ijms20174161

AMA Style

Chang T, Ho H-L, Hsu S-J, Chang C-C, Tsai M-H, Huo T-I, Huang H-C, Lee F-Y, Hou M-C, Lee S-D. Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats. International Journal of Molecular Sciences. 2019; 20(17):4161. https://doi.org/10.3390/ijms20174161

Chicago/Turabian Style

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. 2019. "Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats" Int. J. Mol. Sci. 20, no. 17: 4161. https://doi.org/10.3390/ijms20174161

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