Glucobrassicin metabolites ameliorate the development of portal hypertension and cirrhosis in bile duct-ligated rats

Ting Chang, Hsin Ling Ho, Shao Jung Hsu, Ching Chih Chang*, Ming Hung Tsai, Teh Ia Huo, Hui Chun Huang, Fa Yauh Lee, Ming Chih Hou, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Patients suffering fromliver cirrhosis are often complicatedwith 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 3,30-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, andmesenteric proangiogenic factors protein expressionswere evaluated. Compared to vehicle, bothDIMand I3Csignificantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIMsignificantly 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.

Original languageEnglish
Article number4161
JournalInternational Journal Of Molecular Sciences
Volume20
Issue number17
DOIs
StatePublished - 1 Sep 2019

Keywords

  • 3,30-diindolymethane (DIM)
  • Angiogenesis
  • Indole-3-carbinol (I3C)
  • Liver cirrhosis
  • Portosystemic collaterals

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