2'-Hydroxyflavanone ameliorates mesenteric angiogenesis and portal-systemic collaterals in rats with liver fibrosis

I. Fang Hsin, Jing Yi Lee, Teh Ia Huo, Fa Yauh Lee*, Hui Chun Huang, Shao Jung Hsu, Sun Sang Wang, Hsin Ling Ho, Han Chieh Lin, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background and Aim: Portal-systemic collaterals lead to dreadful consequences in patients with cirrhosis. Angiogenesis participates in the development of liver fibrosis, hyperdynamic circulation, and portal-systemic collaterals. 2′-Hydroxyflavanone (2′-HF), one of the citrus fruits flavonoids, is known to have antiangiogenesis effect without adverse response. However, the relevant effects in liver fibrosis have not been surveyed. Methods: Male Wistar rats received thioacetamide (TAA, 100mg/kg tiw, i.p.) for 6weeks to induce liver fibrosis. On the 29th to 42nd day, rats randomly received 2′-HF (100mg/kg, qod, i.p.) or vehicle (corn oil). On the 43rd day, after hemodynamic measurements, the followings were surveyed: (i) severity of collaterals; (ii) mesenteric angiogenesis; (iii) mesenteric proangiogenic factors protein expressions; (iv) Mesenteric vascular endothelial cells apoptosis; and (v) Mesenteric expressions of proteins regulating apoptosis. Results: Compared with the vehicle group, 2′-HF did not significantly change body weight, mean arterial pressure, heart rate, and portal pressure in TAA rats. 2′-HF significantly alleviated the severity of collaterals, but the mesenteric phospho-ERK, ERK, phospho-Akt, Akt, COX1, COX2, VEGF, and VEGFR-2 protein expressions were not altered. The apoptotic index of 2′-HF group was significantly higher and the mesenteric protein expressions of pro-apoptotic factors, NFkB 50, NFkB 65, Bax, phospho-p53, 17kD cleaved caspase 3, and 17kD casepase 3 were up-regulated. Conclusions: 2′-HF does not influence the hemodynamics but alleviated the severity of collaterals in rats with liver fibrosis and early portal hypertension. This is, at least partly, attributed to enhanced apoptosis of mesenteric vascular endothelial cells.

Original languageEnglish
Pages (from-to)1045-1051
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume31
Issue number5
DOIs
StatePublished - 1 May 2016

Keywords

  • Angiogenesis
  • Flavonoids
  • Liver fibrosis
  • Portal-systemic collaterals
  • Vascular endothelial growth factor

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