• Hsin-Ling Ho, Teh-Ia Huo, Ting Chang, Wen-Shin Lee, I-Fang Hsin, Fa-Yauh Lee, Hui-Chun Huang, Ming-Chih Hou, and Shou-Dong Lee.
• Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department and Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
• J Chin Med Assoc. 2017 Sep 1; 80 (9): 539-550.

BackgroundLiver inflammation may induce fibrogenesis, cirrhosis and portal hypertension. Liver cirrhosis is characterized by increased intrahepatic resistance and enhanced vasoconstrictive response. The splanchnic vasodilatation, angiogenesis and portosystemic collaterals formation further bring about lethal complications. Ascorbate is a potent antioxidant with anti-inflammation, anti-fibrosis, and anti-angiogenesis effects. However, the relevant influences in chronic liver injury have not been sufficiently explored.MethodsChronic liver injury was induced in Spraque-Dawley rats with common bile duct ligation (BDL). Ascorbate (250 mg/kg/day, oral gavage) or vehicle was administered starting on the 1st day after operation. On the 8th (hepatitis) and 29th (cirrhosis) day, serum biochemistry parameters, hepatic concentrations of lipid peroxidation-related substances, protein expressions of α-SMA, TGF-β, iNOS, eNOS, p-eNOS-Ser1177, p-eNOS-Thr496, VEGF, VEGFR2, p-VEGFR2, and liver histology were evaluated. In three series of paralleled groups, rats treated with 28-day ascorbate or vehicle received hemodynamic measurements, hepatic and collateral vasoresponsiveness perfusion experiments, mesenteric CD31 immunofluorescence staining, and Western blot analyses of mesenteric VEGF, VEGFR2, pVEGFR2, PDGF, PDGFβ, COX1, COX2, eNOS, p-eNOS-Thr495, p-eNOS-Ser1177 protein expressions. In another series, the severity of portosystemic shunting was evaluated.ResultsAscorbate did not influence hepatitis, oxidative stress, fibrosis, and hemodynamic parameters in BDL rats. The intrahepatic and collateral vasoresponsiveness were not affected, either from direct incubation or acute treatment with ascorbate. Furthermore, the mesenteric angiogenesis and severity of shunting were not influenced.ConclusionThe oxidative stress, fibrosis, hemodynamic derangements, angiogenesis and vascular functional changes in BDL-induced chronic liver injury may be too overwhelming to be modulated by ascorbate.Copyright © 2017. Published by Elsevier Taiwan LLC.

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