Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation

2021 ◽  
pp. 096452842110392
Author(s):  
Yu-Sheng Chen ◽  
Chorng-Kai Wen ◽  
Geng-Hao Liu ◽  
Tzung-Yan Lee
Keyword(s):  
Portal Hypertension ◽  
Growth Factor ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Portal Pressure ◽  
Contractile Responses ◽  
Hyperdynamic Circulation ◽  
Duct Ligation ◽  
Tnf Α ◽  
Cox 1

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

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.

The Effect of Insulin-like Growth Factor-I on Hepatocyte Apoptosis After Bile Duct Ligation in Rat

2006 ◽  
Vol 51 (12) ◽  
pp. 2220-2224 ◽  
Author(s):  
Shyr-Ming Sheen-Chen ◽  
Hsin-Tsung Ho ◽  
Lu Chia-Pei ◽  
Kuo-Sheng Hung ◽  
Hock-Liew Eng
Keyword(s):  
Growth Factor ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Insulin Like Growth Factor ◽  
Hepatocyte Apoptosis ◽  
Factor I ◽  
Duct Ligation ◽  
Growth Factor I

Common bile duct ligation in the rat: a model of intrapulmonary vasodilatation and hepatopulmonary syndrome

1997 ◽  
Vol 272 (4) ◽  
pp. G779-G784 ◽  
Author(s):  
M. B. Fallon ◽  
G. A. Abrams ◽  
J. W. McGrath ◽  
Z. Hou ◽  
B. Luo
Keyword(s):  
Portal Hypertension ◽  
Bile Duct ◽  
Gas Exchange ◽  
Common Bile Duct ◽  
Lung Injury ◽  
Bile Duct Ligation ◽  
Hepatopulmonary Syndrome ◽  
Common Bile Duct Ligation ◽  
Arterial Blood ◽  
Duct Ligation

Hepatopulmonary syndrome (HPS) causes impaired oxygenation due to intrapulmonary vasodilatation in patients with cirrhosis. Chronic common bile duct ligation (CBDL) in the rat results in gas-exchange abnormalities similar to HPS, but intrapulmonary vasodilatation has not been evaluated. We assess intrapulmonary vasodilatation, measured in vivo, after CBDL. Sham, 2- and 5-wk CBDL, and 3-wk partial portal vein ligated (PVL) rats had hepatic and lung injury, portal pressure, and arterial blood gases assessed. The pulmonary microcirculation was evaluated by injecting microspheres (size range 5.5-10 microm) intravenously and measuring the size and number of microspheres bypassing the lungs in arterial blood. CBDL animals developed progressive hepatic injury and portal hypertension accompanied by gas-exchange abnormalities and intrapulmonary vasodilatation. PVL animals, with a similar degree of portal hypertension, did not develop intrapulmonary vasodilatation or abnormal gas exchange. No lung injury was observed. CBDL, but not PVL, causes progressive intrapulmonary vasodilatation, which accompanies worsening arterial gas exchange. These findings validate CBDL as a model to study HPS.

Early colchicine administration reduces hepatic fibrosis and portal hypertension in rats with bile duct ligation

1993 ◽  
Vol 19 (1) ◽  
pp. 90-94 ◽  
Author(s):  
Jorge L. Poo ◽  
Gérard Feldmann ◽  
Alain Moreau ◽  
Christophe Gaudin ◽  
Didier Lebrec
Keyword(s):  
Portal Hypertension ◽  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation

Renal perfusion in dogs with experimental hepatic cirrhosis: role of prostaglandins

1983 ◽  
Vol 245 (4) ◽  
pp. F521-F529
Author(s):  
M. Levy ◽  
M. J. Wexler ◽  
C. Fechner
Keyword(s):  
Portal Hypertension ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Renin Angiotensin System ◽  
Renal Perfusion ◽  
Venous Hypertension ◽  
Prostaglandin Synthesis ◽  
Portacaval Anastomosis ◽  
Duct Ligation ◽  
Pah Clearance

Increased renal production of prostaglandins are thought to be important for the maintenance of kidney blood flow in advanced cirrhosis. In alert, unanesthetized dogs with chronic cirrhosis and ascites, produced by bile duct ligation, we measured inulin and p-aminohippurate (PAH) clearance before and after the intravenous administration of 2 mg/kg indomethacin, an inhibitor of prostaglandin production. Inulin and PAH clearance declined by 42 and 43%, respectively. This decline in renal perfusion was not associated with changes in blood pressure or cardiac output. If portal hypertension was prevented by creating an end-side portacaval anastomosis at the time of bile duct ligation, indomethacin was without effect on renal perfusion whether or not the dog had ascites. If ascites was completely mobilized in cirrhotic dogs with portal venous hypertension with the aid of a LeVeen valve, indomethacin depressed inulin and PAH clearance as usual during the steady-state period once all ascites had been removed. An attempt was made to determine some of the factors mediating the apparent increase in renal prostaglandin synthesis by administering various pharmacological antagonists. The inhibition of angiotensin effect with saralasin and the inhibition of kallikrein with aprotinin prevented the usual indomethacin effect. It is concluded that portal hypertension, but not a “sick liver per se, in cirrhosis activates the renin-angiotensin system to both produce renal vasoconstriction and stimulate prostaglandin synthesis, thereby normalizing renal perfusion. Renal kallikrein also appears to play a role, probably by augmenting renin release.

Effects of simvastatin, pentoxifylline and spironolactone on hepatic fibrosis and portal hypertension in rats with bile duct ligation

1997 ◽  
Vol 26 (6) ◽  
pp. 1363-1371 ◽  
Author(s):  
Frédéric Oberti ◽  
Christophe Pilette ◽  
Hervé Rifflet ◽  
Moussa Y. Maïga ◽  
Alain Moreau ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation

Prevention of portal hypertension by propanolol and spironolactone in rats with bile duct ligation

1997 ◽  
Vol 26 (1) ◽  
pp. 167-173 ◽  
Author(s):  
Frédéric Oberti ◽  
Hervé Rifflet ◽  
Moussa Y. Maïga ◽  
Christophe Pilette ◽  
Yves Gallois ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Duct Ligation

Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in rats with long-term bile duct ligation

Hepatology ◽  
1993 ◽  
Vol 18 (2) ◽  
pp. 389-393 ◽  
Author(s):  
Mercedes Fernández ◽  
Pilar Pizcueta ◽  
Juan Carlos García-Pagán ◽  
Faust Feu ◽  
Isabel Cirera ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Duct Ligation ◽  
Portal Pressure ◽  
Splanchnic Hemodynamics ◽  
Duct Ligation ◽  
Serotonergic Antagonist

scholarly journals Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice

2019 ◽  
Vol 20 (17) ◽  
pp. 4181
Author(s):  
Zi-Yu Chang ◽  
Chin-Chang Chen ◽  
Hsuan-Miao Liu ◽  
Yuan-Chieh Yeh ◽  
Tung-Yi Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Smooth Muscle Actin ◽  
Matrix Metalloproteinase 2 ◽  
Positive Effects ◽  
Duct Ligation

The purpose of this study was to investigate whether Ger-Gen-Chyn-Lian-Tang (GGCLT) suppresses oxidative stress, inflammation, and angiogenesis during experimental liver fibrosis through the hypoxia-inducible factor-1α (HIF-1α)-mediated pathway. Male C57BL/6 mice were randomly assigned to a sham-control or bile duct ligation (BDL) group with or without treatment with GGCLT at 30, 100, and 300 mg/kg. Plasma alanine aminotransferase (ALT) levels were analyzed using a diagnostic kit. Liver histopathology and hepatic status parameters were measured. Compared to control mice, the BDL mice exhibited an enlargement in liver HIF-1α levels, which was suppressed by 100 and 300 mg/kg GGCLT treatments (control: BDL: BDL + GGCLT-100: BDL + GGCLT-300 = 0.95 ± 0.07: 1.95 ± 0.12: 1.43 ± 0.05: 1.12 ± 0.10 fold; p < 0.05). GGCLT restrained the induction of hepatic hydroxyproline and malondialdehyde levels in the mice challenged with BDL, further increasing the hepatic glutathione levels. Furthermore, in response to increased hepatic inflammation and fibrogenesis, significant levels of ALT, nuclear factor kappa B, transforming growth factor-β, α-smooth muscle actin, matrix metalloproteinase-2 (MMP-2), MMP-9, and procollagen-III were found in BDL mice, which were attenuated with GGCLT. In addition, GGCLT reduced the induction of angiogenesis in the liver after BDL by inhibiting vascular endothelial growth factor (VEGF) and VEGF receptors 1 and 2. In conclusion, the anti-liver fibrosis effect of GGCLT, which suppresses hepatic oxidative stress and angiogenesis, may be dependent on an HIF-1α-mediated pathway.

scholarly journals Antioxidant and Anti-Inflammatory Effects of Origanum majorana L. Methanolic Extract on Bile Duct Ligation in Male Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Izadpanah Gheitasi ◽  
Nikta Motaghi ◽  
Hossein Sadeghi ◽  
Heibatollah Sadeghi ◽  
Zahra Moslemi ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Duct Ligation ◽  
Methanolic Extract ◽  
Control Group ◽  
Histopathological Changes ◽  
Sham Control ◽  
Duct Ligation ◽  
Tnf Α ◽  
Sham Control Group ◽  
Origanum Majorana

Introduction. Cholestasis is caused by malfunction of the hepatobiliary system. This disorder is the result of the accumulation of bile fatty acids and other toxins in the liver. The aim of the current study was to investigate the antioxidative and hepatoprotective effects of methanolic extract of Origanum majorana L. (OM) on hepatic disorder and tissue damage induced by bile duct ligation (BDL) in rats. Materials and methods. Twenty-eight male Wistar rats were randomly divided into 4 groups including sham control group received vehicle (SC-V), bile duct ligation received vehicle (BDL-V), bile duct ligation group received OM extract (BDL + OM), and sham control group received OM extract (SC + OM). One day after surgery, the animals received vehicle or methanolic extract of OM 300 mg/kg/day for 7 consecutive days by oral gavage. Finally, the animals were anesthetized and the blood samples were collected from each animal. After sacrificing of animals, liver tissue from each rat was removed and divided into three parts: one part was used for preparing of homogenized tissue, one part was fixed in 10% neutral formalin for histopathology examination, and the third part was kept in liquid nitrogen for gene expression analysis. Biomarkers of oxidative stress in the liver tissue and serum, as well as histopathological changes of the liver, were assessed. Also, the gene expression of IL-1, TNF-α, TGF-β, and α-SMA has been measured. Results. The results showed that BDL-V significantly increased the activity of ALT, AST, ALP, and total bilirubin compared to the SC-V group. The oxidative stress markers such as MDA and FRAP significantly increased due to BDL, while the CAT activity reduced in the BDL-V group compared to SC-V group. Oral treatment with OM reduced ALT and AST activity, although it was not statistically significant. OM treatment considerably increased the activity of CAT compared to BDL group. BDL-V induced a significant histological change in the liver, while treatment with OM at a dose of 300 mg/kg showed a minor effect on histopathological changes. In addition, the mRNA of IL-1, TNF-α, TGF-β, and α-SMA significantly increased in the BDL-V group, while treatment with OM only significantly reduced TGF-β in comparison with BDL-V rats. Conclusions. The results of the present study showed that oral administration of OM extract had a moderate protective effect on cholestasis due to BDL. Indeed, more studies with different doses of extract are needed to confirm this finding.

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