Lycopene treatment improves intrahepatic fibrosis and attenuates pathological angiogenesis in biliary cirrhotic rats. Issue 4 (6th April 2022)

• Record Type: Journal Article
• Authors: Huang, Hui-Chun; Hsu, Shao-Jung; Chang, Ching-Chih; Kao, Yun-Chieh; Chuang, Chiao-Lin; Hou, Ming-Chih; Lee, Fa-Yauh
• Is Part Of: Journal of the Chinese Medical Association. Volume 85:Issue 4(2022)
• Page Start: 414
• Page End: 420
• Publication Date: 2022-04-06
• Subjects: Angiogenesis -- Hyperdynamic circulation -- Liver cirrhosis -- Lycopene -- Portal hypertension; Medicine -- Periodicals; 610.5
• DOI: 10.1097/JCMA.0000000000000699
• Languages: English
• ISSNs: 1726-4901

Abstract

Abstract : Background: Liver cirrhosis is characterized by liver fibrosis and pathological angiogenesis, which results in hyperdynamic circulation, portal-systemic collateral vascular formation, and abnormal angiogenesis. Lycopene is a nutrient mostly found in tomatoes. The beneficial effects of lycopene include anti-inflammation, anti-oxidation, anti-fibrosis, and anti-angiogenesis; however, the association between liver cirrhosis and pathological angiogenesis has yet to be studied. This study aimed to investigate the effects of lycopene on biliary cirrhotic rats. Methods: The efficacy of lycopene treatment in common bile duct ligation (BDL)-induced biliary cirrhotic rats was evaluated. Sham-operated rats served as surgical controls. Lycopene (20 mg/kg/day, oral gavage) or vehicle was administered to BDL or sham-operated rats for 4 weeks, after which the hemodynamics, liver biochemistry, portal-systemic shunting, liver and mesenteric angiogenesis, and hepatic angiogenesis-related protein expressions were examined. Results: Lycopene alleviated hyperdynamic circulation as evidenced by decreased cardiac index and increased peripheral vascular resistance ( p < 0.05), but it did not affect portal pressure or liver biochemistry in the BDL rats ( p > 0.05). Lycopene significantly diminished the shunting degree of portal-systemic collaterals ( p = 0.04) and mesenteric vascular density ( p = 0.01), and also ameliorated intrahepatic angiogenesis and liver fibrosis. In addition, lycopene upregulated endothelial nitric oxide synthase, protein kinase B (Akt) and phosphatidylinositol 3-kinases (PI3K), and downregulated vascular endothelial growth factor receptor 2 (VEGFR-2) protein expressions ( p < 0.05) in the livers of the BDL rats. Conclusion: Lycopene ameliorated liver fibrosis, hyperdynamic circulation, and pathological angiogenesis in biliary cirrhotic rats, possibly through the modulation of intrahepatic Akt/PI3K/eNOS and VEGFR-2 pathways.