scholarly journals New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats

2022 ◽  
Vol 15 (1) ◽  
pp. 85
Author(s):  
Xia Niu ◽  
Xiaomei Wang ◽  
Bingyu Niu ◽  
Yucheng Wang ◽  
Hongwei He ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Liver Function ◽  
Hepatic Fibrosis ◽  
Oral Bioavailability ◽  
Bile Duct Ligation ◽  
Aqueous Solubility ◽  
Release Behavior ◽  
Drug Release Behavior ◽  
Duct Ligation

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.

LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice

2006 ◽  
Vol 290 (6) ◽  
pp. G1318-G1328 ◽  
Author(s):  
Fuyumi Isayama ◽  
Ian N. Hines ◽  
Michael Kremer ◽  
Richard J. Milton ◽  
Christy L. Byrd ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Wild Type ◽  
Hepatic Macrophages ◽  
Duct Ligation ◽  
Lps Signaling ◽  
Experimental Cholestasis

Although it is clear that bile acid accumulation is the major initiator of fibrosis caused by cholestatic liver disease, endotoxemia is a common side effect. However, the depletion of hepatic macrophages with gadolinium chloride blunts hepatic fibrosis. Because endotoxin is a key activator of hepatic macrophages, this study was designed to test the hypothesis that LPS signaling through CD14 contributes to hepatic fibrosis caused by experimental cholestasis. Wild-type mice and CD14 knockout mice (CD14−/−) underwent sham operation or bile duct ligation and were killed 3 wk later. Measures of liver injury, such as focal necrosis, biliary cell proliferation, and inflammatory cell influx, were not significantly different among the strains 3 wk after bile duct ligation. Markers of liver fibrosis such as Sirius red staining, liver hydroxyproline, and α-smooth muscle actin expression were blunted in CD14−/− mice compared with wild-type mice after bile duct ligation. Despite no difference in lymphocyte infiltration, the macrophage/monocyte activation marker OX42 (CD11b) and the oxidative stress/lipid peroxidation marker 4-hydroxynonenal were significantly upregulated in wild-type mice after bile duct ligation but not in CD14−/− mice. Increased profibrogenic cytokine mRNA expression in the liver after bile duct ligation was significantly blunted in CD14−/− mice compared with the wild type. The hypothesis that LPS was involved in experimental cholestatic liver fibrosis was tested using mice deficient in LPS-binding protein (LBP−/−). LBP−/− mice had less liver injury and fibrosis (Siruis red staining and hydroxyproline content) compared with wild-type mice after bile duct ligation. In conclusion, these data demonstrate that endotoxin in a CD14-dependent manner exacerbates hepatic fibrogenesis and macrophage activation to produce oxidants and cytokines after bile duct ligation.

scholarly journals Effect of vitamin C inhibiting liver fibrosis and lipid peroxidation in biliary obstruction of Wistar rats

2020 ◽  
Vol 7 (9) ◽  
pp. 2830
Author(s):  
Widhitomo . ◽  
Nurhayat Usman ◽  
Reno Rudiman
Keyword(s):  
Lipid Peroxidation ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Vitamin C ◽  
Hepatic Fibrosis ◽  
Biliary Obstruction ◽  
Wistar Rats ◽  
Bile Duct Ligation ◽  
Albino Rats ◽  
Duct Ligation

Background: The aim of this study was to evaluate the potential inhibiting effects of vitamin C as an antioxidant against liver fibrosis and lipid peroxidation in the bile duct ligation- induced biliary obstruction of Wistar rats.Methods: A total of 25 male Wistar albino rats were divided into five groups: sham operated, control (bile duct ligation/BDL) without given vitamin C, BDL with vitamin C 75 mg, BDL with vitamin C 150 mg, and BDL with vitamin C 225 mg. Each group contained 5 animals. Vitamin C was given orally on day 3 after operation and after 14 days following vitamin C administration, all animals were performed laparotomy to obtain liver tissue samples for histopathological investigation of liver fibrosis and blood samples for malondialdehyde (MDA) as lipid peroxidation measurement.Results: The changes demonstrating hepatic fibrosis including moderate to markedly thickened wall of central veins, localized to diffuse perisinusoidal fibrosis, enlarged portal track, increased number of septa, and thickened width of septa were observed in BDL groups. MDA measurement were also observed in all groups. Treatment of biliary obstruction in BDL groups with vitamin C given orally attenuated liver damage. Both the MDA measurement and histopathologic investigation of hepatic fibrosis were observed to be reduced with the vitamin C treatment.Conclusions: Our data indicate that vitamin C inhibited liver fibrosis and lipid peroxidation in bile duct ligation-induced biliary obstruction of Wistar rats. 

Adenoviral CCN3/NOV gene transfer fails to mitigate liver fibrosis in an experimental bile duct ligation model because of hepatocyte apoptosis

2012 ◽  
Vol 32 (9) ◽  
pp. 1342-1353 ◽  
Author(s):  
Erawan Borkham-Kamphorst ◽  
Sebastian Huss ◽  
Eddy Leur ◽  
Ute Haas ◽  
Ralf Weiskirchen
Keyword(s):  
Bile Duct ◽  
Gene Transfer ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Hepatocyte Apoptosis ◽  
Duct Ligation

scholarly journals PAI-1 deficiency reduces liver fibrosis after bile duct ligation in mice through activation of tPA

FEBS Letters ◽  
2007 ◽  
Vol 581 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Hongtao Wang ◽  
Yan Zhang ◽  
Robert O. Heuckeroth
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Pai 1

scholarly journals MicroRNA-29a Alleviates Bile Duct Ligation Exacerbation of Hepatic Fibrosis in Mice through Epigenetic Control of Methyltransferases

2017 ◽  
Vol 18 (1) ◽  
pp. 192 ◽  
Author(s):  
Ya-Ling Yang ◽  
Feng-Sheng Wang ◽  
Sung-Chou Li ◽  
Mao-Meng Tiao ◽  
Ying-Hsien Huang
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Epigenetic Control ◽  
Duct Ligation

scholarly journals Vitamin A Supplementation Alleviates Extrahepatic Cholestasis Liver Injury through Nrf2 Activation

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Guiyang Wang ◽  
Peng Xiu ◽  
Fu Li ◽  
Cheng Xin ◽  
Kewei Li
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Liver Function ◽  
Vitamin A ◽  
Western Blotting ◽  
Bile Duct Ligation ◽  
Retinyl Palmitate ◽  
Binding Activity ◽  
Extrahepatic Cholestasis ◽  
Duct Ligation

Aim. To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats.Methods. Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays.Results. Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.Conclusion. Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats

2003 ◽  
Vol 285 (5) ◽  
pp. G1004-G1013 ◽  
Author(s):  
Zhi Zhong ◽  
Matthias Froh ◽  
Mark Lehnert ◽  
Robert Schoonhoven ◽  
Liu Yang ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Smooth Muscle Actin ◽  
Control Diet ◽  
Free Radical Scavengers ◽  
Bile Duct Proliferation ◽  
Duct Ligation ◽  
Experimental Cholestasis

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1–2 days, and fibrosis developed 2–3 wk after bile duct ligation. Additionally, procollagen-α1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of α-smooth muscle actin and transforming growth factor-β and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45–73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.

scholarly journals Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in rats

2008 ◽  
Vol 38 (7) ◽  
pp. 727-735 ◽  
Author(s):  
Kazunori Maeda ◽  
Masahiko Koda ◽  
Tomomitsu Matono ◽  
Takaaki Sugihara ◽  
Satoru Yamamoto ◽  
...  
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Preventive Effects

Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis

2015 ◽  
Vol 308 (2) ◽  
pp. G112-G120 ◽  
Author(s):  
Shirley Abramovitch ◽  
Efrat Sharvit ◽  
Yosef Weisman ◽  
Amir Bentov ◽  
Eli Brazowski ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Active Form ◽  
Preventive Treatment ◽  
Antifibrotic Effect ◽  
Duct Ligation

1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis.

Sign in / Sign up

Export Citation Format

Share Document