Curcumin ameliorates intrahepatic angiogenesis and capillarization of the sinusoids in carbon tetrachloride-induced rat liver fibrosis.
Neoangiogenesis and the development of an abnormal angio-architecture in the liver are strongly linked with progressive fibrogenesis. This study aimed to evaluate the ability of curcumin to protect liver fibrosis-associated angiogenesis and capillarization of the sinusoids in experimental rats. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl₄) with or without curcumin for 6 weeks. The results suggest that curcumin treatment markedly attenuated CCl₄-induced liver fibrosis, as assessed by histology and hydroxyproline content, and inhibited hepatic stellate cell activation. Curcumin ameliorated hepatic angiogenesis, as assessed by measuring microvessel density using Von Willebrand factor staining and by examining the expression of the endothelial cell markers CD31 and vascular endothelial growth factor receptor (VEGFR)-2 in the livers. Pathologic remodeling of liver sinusoidal capillarization, as assessed by electron-microscopic analysis of Disse's space and by evaluation of the levels of basement membrane protein expression, was also attenuated by curcumin administration. The intrahepatic gene or protein expression of hypoxia-inducible factor-1α, VEGFR-1, placental growth factor, and cyclooxygenase-2 decreased with treatment with curcumin in fibrotic rats. In conclusion, curcumin ameliorates hepatic angiogenesis and sinusoidal capillarization in CCl₄-induced rat liver fibrosis through suppressing multiple proangiogenic factors.
['Yao|Qunyan|Q|', 'Lin|Yizheng|Y|', 'Li|Xi|X|', 'Shen|Xizhong|X|', 'Wang|Jiyao|J|', 'Tu|Chuantao|C|']
D020533:Angiogenesis Inhibitors D000818:Animals D015153:Blotting, Western D002196:Capillaries D002252:Carbon Tetrachloride Poisoning D003474:Curcumin D006504:Hepatic Veno-Occlusive Disease D006909:Hydroxyproline D007150:Immunohistochemistry D008099:Liver D008103:Liver Cirrhosis D008297:Male D046529:Microscopy, Electron, Transmission D051381:Rats D017207:Rats, Sprague-Dawley D060888:Real-Time Polymerase Chain Reaction
Curcumin Angiogenesis Liver fibrosis carbon tetrachloride hepatic stellate cells von Willebrand factor vascular endothelial growth factor vascular endothelial growth factor receptor Sinusoidal capillarization hypoxia-inducible factor-1α placental growth factor cyclooxygenase-2 CCl(4) COX-2 Cirrhosis ECM HIF-1α HMGB1 HSC PlGF SECs TEM TGF-β1 TNF-α VEGF VEGFR alpha-smooth muscle actin extracellular matrix high-mobility group box 1 sinusoidal endothelial cells transforming growth factor-beta1 transmission electron microscopy tumor necrosis factor vWF α-SMA