Biliary Obstruction In Rats Research Articles

Dodder (Cuscuta sp.) Extract Ameliorates Liver Fibrosis in Bile Duct-Ligated Rats

Objective: The aim is to examine the possible protective effect of Cuscuta sp. extract against liver damage induced by biliary obstruction in rats. Materials and Methods: To induce biliary obstruction, the bile duct ligation (BDL) method was used. Sprague Dawley rats were allocated to 4 groups: Control (C), Cuscuta (CUS), bile duct ligation (BDL), and bile duct ligation + Cuscuta (BDL+CUS). Control and BDL rats were given physiological saline (SF), while CUS and BDL+CUS groups were administered 250 mg/ kg of Cuscuta extract by oral gavage. At the end of 28th day, the rats were decapitated, serum and tissue samples were collected, and aspartate aminotransferase (AST), alanine transaminase (ALT), and direct and total bilirubin (DB and TB) levels were determined in blood samples. In liver tissues, transforming growth factor-β (TGF-β), 8-hydroxyguanosine (8-OHdG), hydroxyproline, and sodium–potassium ATPase (Na+/K+-ATPase) levels were determined. Results: Serum samples of rats with cholestasis had high ALT, AST, DB, and TB levels, while TGF-β, 8-OHdG, and hydroxyproline concentrations were found to be significantly high in tissues. Hepatic Na+/K+-ATPase levels were decreased through biliary obstruction. Biochemical parameters were drastically reversed by Cuscuta care; also, this was supported histologically. Conclusion: Results showed that Cuscuta extract, through its antioxidant and anti-inflammatory properties, provided protection against oxidative injury by biliary obstruction. Also, these results confirm the traditional use of Cuscuta sp. as hepatoprotective.

The ameliorative effect of vinpocetine on liver fibrosis and bone changes in the bile-duct ligated rat

Vinpocetine is a drug that is widely used to treat vascular cognitive disorders in the old age. The drug has been shown to protect against hepatocellular damage caused by carbon tetrachloride in rats. In this study, vinpocetine was investigated for its ability to improve cholestatic hepatic injury and bone changes associated with bile duct ligation in rats. Rats with biliary obstruction induced by double ligation and section of the common bile duct were randomly and blindly assigned to receive either vinpocetine (2.1, 4.2, 8.4 mg/kg) or saline once a day orally, starting one day after surgery and continued for one month thereafter. At the end of the treatment period, rats were killed and analyzed for blood biochemistry, liver and bone histopathology. Compared to their sham-treated counterparts, bile duct-ligated (BDL) rats exhibited markedly elevated serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) as well markedly raised serum bilirubin level. Histopathological examination of BDL rats revealed focal necrosis, degenerated hepatocytes, bile duct hyperplasia and inflammatory cell infiltrates. Histochemical staining using Feulgen and Periodic acid-Schiff’s (PAS) staining showed depletion of liver glycogen and markedly decreased deoxyribonucleic acid (DNA) content in hepatocytes. Reduced osteocyte cellularity and few areas of regenerating bone were observed in BDL rats. The administration of vinpocetine to BDL rats resulted in dose-dependent decrease in serum ALT, AST, ALP activities by 33.6-64.4%, 17.5-43.9% and 26.5%-39.2%, respectively. Serum bilirubin decreased by 19% after 8.4 mg/kg of vinpocetine. The drug also resulted in amelioration of the pathological changes in the liver, increased glycogen and DNA content of hepatocytes and improved bone cellularity and increased bone regeneration dose-dependently. These findings suggest a beneficial effect for vinpocetine on liver damage and bone changes caused by biliary obstruction in rats.

Effects of Probiotic Use on Bacterial Translocation in Created Rat Models with Biliary Obstructions.

The aim of this study was to investigate the protective effects of the combined use of probiotic strains on the development of bacterial translocation in addition to liver and intestinal tissue damage due to biliary obstruction in rats. Here, 3 groups each consisting of 10 rats were created:group 1 (sham group), group 2 (obstructive jaundice), and group 3 (obstructive jaundice+probiotic). Groups 1 and 2 were given 1 cc physiological saline solution by oral gavage twice a day; group 3 was given a probiotic solution that included Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Enterococcus faecium, and Bifidobacterium longum microorganisms by oral gavage twice a day. Markers for liver damage were also found to be significantly improved (p<0.05) in the treatment group (group 3). When compared with groups 2 and 3 in terms of liver histology, damage was found to be significantly more severe in group 2 (p<0.01). With regard to ileal villous depth and ileal inflammation, the pathology was found to be significantly more severe in group 2 than that in group 3 (p<0.05). In blood, spleen, and mesenteric lymph node cultures, group 2 showed a microbiological growth rate of 33.8-58.8%, whereas group 3 showed a microbiological growth rate of 14.3-28.6%. This reduction was evaluated to be statistically significant (p<0.05). Our study showed that the combined use of a probiotic in bile duct obstructions reduced bacterial translocation and alleviated pathological changes arising in the liver and terminal ileum histology.

The effect of fractal-like mechanical ventilation on vital signs in a rat model of acute-on-chronic liver failure

Objective: The network of interactions between different organs is impaired in liver cirrhosis. Liver cirrhosis is associated with multi-system involvement, which eventually leads to multiple organ failure. This process is accelerated by a precipitating factor such as bacterial infection, which leads to respiratory distress, circulatory shock, neural dysfunction and very high mortality. Cirrhotic patients often have blunted respiratory sinus arrhythmia and impaired cardio-respiratory variability. Fractal-like mechanical ventilation is reported to enhance respiratory sinus arrhythmia and attenuate respiratory distress in experimental models. In the present study we hypothesise that fractal-like mechanical ventilation may improve the outcome of cirrhotic rats with multiple organ failure. Approach: Cirrhosis was induced by chronic biliary obstruction in rats. Acute multiple organ failure was induced by intraperitoneal injection of bacterial endotoxin in cirrhotic rats. The effect of conventional mechanical ventilation (with constant tidal volume and respiratory rate) or fractal-like ventilation (with the same average but variable tidal volume and respiratory rate) were assessed on vital signs, oxygen saturation and plasma alanine aminotransferase in anaesthetised cirrhotic rats. Main results: We demonstrated that fractal-like mechanical ventilation was accompanied by improved oxygen saturation, reduced heart rate and decreased liver injury following injection of bacterial endotoxin. Moreover, variable mechanical ventilation in cirrhotic rats reduced mortality and prevented a fall in short-term heart rate variability following endotoxin challenge in comparison with rats with constant mechanical ventilation. Significance: We suggest further investigations into the beneficial effects of fractal-like ventilation strategy in critically ill patients with liver failure requiring organ support and mechanical ventilation.

Protective effects of rutin on liver injury induced by biliary obstruction in rats

Rutin has been shown to possess beneficial health effects, including hepatoprotection. However, to date, it has not been demonstrated to have a hepatoprotective effect against cholestatic liver injury. This is the first report to show a protective effect of rutin on cholestatic liver injury. Cholestasis was produced by bile duct ligation (BDL) in male Sprague–Dawley rats for 3 weeks. Daily oral administration of rutin was started 1 week before injury and was maintained for 4 weeks. In comparison with the control group, the BDL group showed liver injury as evidenced by histological changes and elevation in serum biochemicals, ductular reaction, fibrosis, inflammation, and oxidative stress. These pathophysiological changes were attenuated by rutin supplementation. Rutin alleviated BDL-induced transforming growth factor β1 (TGF-β1), interleukin-1β, connective tissue growth factor, and collagen expression. The antifibrotic effect of rutin was accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity critical to the fibrogenic potential of TGF-β1. Rutin attenuated BDL-induced oxidative stress, leukocyte accumulation, NF-κB activation, and proinflammatory cytokine production. Further studies demonstrated an inhibitory effect of rutin on the redox-sensitive intracellular signaling molecule extracellular signal-regulated kinase (ERK). Rutin also attenuated BDL-induced reduction in NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and AMP-activated protein kinase (AMPK). Taken together, the beneficial effects of rutin were shown to be associated with antioxidative and anti-inflammatory effects as well as the downregulation of NF-κB and TGF-β/Smad signaling, probably via interference of ERK activation and/or enhancement of Nrf2, HO-1, and AMPK activity.

Tu1959 Effect of Pentadecapeptide BPC 157 on Liver Lesions Induced by Biliary Obstruction in Rats

Tu1959 Effect of Pentadecapeptide BPC 157 on Liver Lesions Induced by Biliary Obstruction in Rats

The protective effect of Nigella sativa oil in the brain of the biliary obstructed rats

ABSTRACT: Oxidative stress is one of the important mechanisms of jaundice induced encephalopathy. The aim of this study was to examine the possible protective effect of Nigella sativa (NS) seed oil against the oxidative stress of brain tissue induced by experimental obstructive jaundice in rats. BiliarY obstruction was performed in male Wistar albino rats by bile duct ligation and scission (BDL). Intragastric NS oil (1 mg/kg p.o.) or saline was administered for 28 days. At the end of the experiment, in the half of the rats the blood brain barrier (BBB) permeability was evaluated by Evans blue (EB) extravasation. Other rats were decapitated and brain tissue samples were obtained for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na+,K+-ATPase activities. ChronIC biliary obstruction caused a significant increase in the BBB permeability which was verified by EB extravasation while this effect was attenuated by NS oil treatment. On the other hand, BDL-induced decrease in brain GSH level and Na+,K+-ATPase activity were elevated back to control level in NS oil-treated BDL group. Increase in tissue MDA level, and MPO activity due to BDL were also attenuated by NS oil treatment. Our results suggest that NS oil treatment protects the brain from oxidative damage following bile duct ligation in rats. This effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation and the restoration of antioxidant status in the tissue. Accordingly, supplementing cirrhotic patients with adjuvant therapy of NS oil may have some benefit against hepatic encephalopathy. KEYWORDS: Nigella, black cumin, bile duct, brain, edema

The protective effect of Nigella sativa oil in the brain of the biliary obstructed rats

The protective effect of Nigella sativa oil in the brain of the biliary obstructed rats

Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats

The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL+received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2ml/kg) once a day intraperitoneally for 2weeks starting 3days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.

Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats

The aim of this study was to examine the preventive and therapeutic effects of thymoquinone (TQ) against cholestatic oxidative stress and liver damage in common bile duct ligated rats. A total of 24 male Sprague-Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received TQ; each group contain 8 animals. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally for 2 weeks starting 3 days prior to BDL operation. To date, no more biochemical and histopathological changes on common bile duct ligated rats by TQ treatment have been reported. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GPx)] activities. TQ treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with TQ attenuated alterations in liver histology. The immunopositivity of alpha smooth muscle actin and proliferating cell nuclear antigen in BDL were observed to be reduced with the TQ treatment. The present study demonstrates that oral administration of TQ in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of TQ may be useful in the preservation of liver function in cholestasis.

The efficiency of CAPE on retardation of hepatic fibrosis in biliary obstructed rats

The aim of this study was to evaluate the possible protective effects of caffeic acid phenethyl ester (CAPE) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. A total of 18 male Sprague-Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received CAPE; each group contain 6 animals. The rats in CAPE treated groups were given CAPE (10 μmol/kg) once a day intraperitoneally (i.p) for 2 weeks starting just after BDL operation. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with CAPE attenuated alterations in liver histology. The proliferating cell nuclear antigen and the activity of TUNEL in the BDL were observed to be reduced with the QE treatment. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme (superoxide dismutase (SOD), glutathione peroxidase (GPx)) activities. CAPE treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The data indicate that CAPE attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of CAPE is associated with antioxidative potential.

Interleukin-10 suppresses hepatic TGF-β1 expression and attenuates hepatocyte apoptosis in biliary-obstructed rats

Interleukin-10 suppresses hepatic TGF-β1 expression and attenuates hepatocyte apoptosis in biliary-obstructed rats

Protective effect of quercetin on liver damage induced by biliary obstruction in rats

The aim of this study was to evaluate the possible protective effects of quercetin (QE) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. A total of 24 male Wistar albino rats were divided into three groups: control, bile duct ligation (BDL) and BDL+received QE; each group contain 8 animals. The rats in QE treated groups were given QE (15mg/kg) once a day intraperitoneally for 4weeks starting 3days prior to BDL operation. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with QE attenuated alterations in liver histology. The alpha smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β1) positive cells and the activity of TUNEL in the BDL were observed to be reduced with the QE treatment. The data indicate that QE attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of QE is associated with antioxidative potential.

Influence of glutamine on morphological and functional changes of liver in the presence of extrahepatic biliary obstruction in rats

To study the influence of glutamine on functional and morphological changes of liver in the extrahepatic biliary obstruction through an experimental model in rats. Seventy Wistar rats were divided into four groups: control (group C) fictitious operation, (group FO), submitted to laparotomy with handling of bile ducts, but without hepatic duct ligation, (group EBO) submitted to laparotomy and hepatic duct ligation, one of them submitted to supplementation with glutamine 2% (group G). The control group consisted of 6 animals. The animals from groups FO, EBO and G were divided into three groups consisting of 6 animals each, being sacrificed at 7, 14 and 21 days after operation, respectively. Blood samples were collected for biochemical analysis and a fragment of liver tissue was collected from the middle lobe for histological analysis. Both for biochemical analysis (BT, aspartate and alanine aminotransferase AST, ALT and alkaline phosphatase FAL) and for histopathological changes (fibrosis, portal inflammation, parenchymal inflammation, hepatocytic changes and duct proliferation), no statistical difference between groups submitted to extrahepatic biliary obstruction (EBO) with and without treatment with glutamine (G) was observed. Glutamine supplementation did not alter the prognosis of liver enzymes and histopathological changes in animals submitted to extrahepatic biliary obstruction.

Anti-fibrotic effects of a hot-water extract from Salvia miltiorrhiza roots on liver fibrosis induced by biliary obstruction in rats.

The anti-fibrotic effects of a hot-water extract form the traditional Chinese medicinal herb Salvia miltiorrhiza (Labiatae) on liver fibrosis induced by biliary obstruction was studied in rats. Liver fibrosis was induced in male Sprague-Dawley rats by bile duct ligation and scission (BDL). After surgery, the hot-water extract of S. miltiorrhiza roots (100 mg kg(-1), p.o.) was administered daily for 28 days. The concentrations of aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin and total cholesterol in serum and hydroxyproline and malondialdehyde contents in liver were significantly increased in BDL rats. Treatment with the extract of S. miltiorrhiza significantly reduced (P < 0.01) the serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and total cholesterol concentrations in BDL rats. The liver hydroxyproline content in BDL rats treated with extract was also reduced to 68% of that in BDL control rats (P < 0.01). The liver malondialdehyde content in BDL rats treated with the extract was also reduced to 47% of that in BDL control rats (P < 0.01). The morphological characteristics of fibrotic livers were improved in BDL rats treated with extract. Immunohistochemical examination of fibrotic liver showed that the extract of S. miltiorrhiza markedly reduced protein expression of alpha-smooth muscle cell-like actin, which indicates that hepatic stellate cell activation was inhibited during liver fibrosis development. The results indicate that the hot-water extract of S. miltiorrhiza roots inhibits fibrosis and lipid peroxidation in rats with liver fibrosis induced by biliary obstruction.

Pomegranate peel extract prevents liver fibrosis in biliary-obstructed rats

Punica granatum L. (pomegranate) is a widely used plant that has high nutritional value. The aim of this study was to assess the effect of chronic administration of pomegranate peel extract (PPE) on liver fibrosis induced by bile duct ligation (BDL) in rats. PPE (50 mg kg(-1)) or saline was administered orally for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin 1 beta) in the serum and antioxidant capacity (AOC) were measured in plasma samples. Samples of liver tissue were taken for measurement of hepatic malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence assay. Serum AST, ALT, LDH and cytokines were elevated in the BDL group compared with the control group; this increase was significantly decreased by PPE treatment. Plasma AOC and hepatic GSH levels were significantly depressed by BDL but were increased back to control levels in the PPE-treated BDL group. Increases in tissue MDA levels and MPO activity due to BDL were reduced back to control levels by PPE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with PPE treatment. Thus, chronic PPE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function. It therefore seems likely that PPE, with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver from fibrosis and oxidative injury due to biliary obstruction.

Protective Effect Of Curcumin On Liver Damage Induced By Biliary Obstruction In Rats

Objective: The aim of this study is to evaluate the possible protective effects of curcumin against cholestatic oxidative stress and liver damage in common bile duct ligated rats. Material and Methods: A total of 18 male Wistar albino rats were divided into three groups: control, common bile duct ligation (BDL) and BDL+curcumin. Each group contained 6 animals. The rats in the curcumin treated group were given curcumin (100 mg/kg) once a day orally for 14 days, starting 3 days prior to BDL operation. Following 14 days of treatment, all the animals were decapitated and liver tissue samples were obtained for histopathological investigation. Results: The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts, including the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas, were observed in BDL group. Treatment of BDL with curcumin attenuated liver damage. Both the elevated alpha smooth muscle actin (aalpha;-SMA), and the activity of TUNEL in the BDL were observed to be reduced with the curcumin treatment. Conclusion: Our data indicate that curcumin reduced BDL-induced cholestatic liver injury, bile duct proliferation, fibrosis.

UP-REGULATED THROMBOXANE PRODUCTION IN THE RAT LIVER WITH BILIARY OBSTRUCTION DOES NOT CONTRIBUTE TO PROMOTE HEPATIC INJURY

This study sought to determine whether in vivo inhibition of thromboxane A2 (TXA2) action contribute to attenuate hepatic damage after bile duct ligation (BDL). Male Wistar rats were assigned to sham operation or BDL. At the time of operation, infusion pump with saline, ozagrel natrium (TXA2 synthase inhibitor), or SQ29548 (TXA2 receptor antagonists) was implanted in the abdominal cavity. Plasma alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, and total bilirubin levels were measured at 4 days after the operation. The levels of plasma TXB2, a stable metabolite of TXA2, were significantly increased after BDL. Gene expression of TXA2 synthase was also significantly upregulated in the liver. Nonetheless, either an inhibition of TXA2 synthesis by ozagrel natrium or a blockade of TXA2 receptor by SQ29548 has no effect in every measured parameter related to hepatic function. These results indicated that despite a highly increased production in the liver, TXA2 is not directly related to the hepatic injury in BDL rats.

The hedgehog pathway regulates remodelling responses to biliary obstruction in rats

Background:Chronic biliary obstruction provokes fibrosis and accumulation of immature ductular cells. This fibroductular reaction resolves following biliary decompression, suggesting that it may also be involved in the repair of biliary...

Grape seed extract reduces oxidative stress and fibrosis in experimental biliary obstruction

The aim of this study was to assess the protective effect of grape seed extract (GSE) against oxidative liver injury and fibrosis induced by biliary obstruction in rats. Wistar albino rats were divided into four groups; control (C), GSE-treated, bile duct ligated (BDL), and BDL and GSE-treated (BDL + GSE) groups. GSE was administered at a dose of 50 mg/kg a day orally for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Tumor necrosis factor-alpha (TNF-alpha) and antioxidant capacity (AOC) were assayed in plasma samples. Liver tissues were taken for determination of the hepatic malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence (CL) assay. Serum AST, ALT, LDH and plasma TNF-alpha were elevated in the BDL group as compared to the control group and were significantly decreased with GSE treatment. Plasma AOC and hepatic GSH level, depressed by BDL, was elevated back to the control level in the GSE-treated BDL group. Increases in tissue MDA level, MPO activity and collagen content due to BDL were also attenuated by GSE treatment. Furthermore, luminol and lucigenin CL values in the BDL group increased dramatically compared to the control and were reduced by GSE treatment. These results suggest that GSE protects the liver from oxidative damage following bile duct ligation in rats. This effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation; thus, restoration of oxidant and antioxidant status in the tissue.