scholarly journals Liver histological, portal flow and plasmatic nitric oxide alterations caused by biliary obstruction and drainage in rats

2008 ◽  
Vol 23 (suppl 1) ◽  
pp. 2-7 ◽  
Author(s):  
Miguel Angel Dias ◽  
Reginaldo Ceneviva ◽  
Jorge Elias Jr. ◽  
Sergio Zucoloto ◽  
Caroline Floreoto Baldo ◽  
...  
Keyword(s):  
Bile Duct ◽  
Biliary Obstruction ◽  
Bile Duct Ligation ◽  
Sham Operation ◽  
Portal Flow ◽  
Histological Alterations ◽  
Duct Occlusion ◽  
Duct Ligation ◽  
Male Wistar Rats ◽  
Periodic Evaluation

PURPOSE: To evaluate liver alterations caused by biliary obstruction and drainage. METHODS: Thirty-nine male Wistar rats were randomly distributed in 4 groups: BO (n=18) bile duct ligation for 20 days, with a periodic evaluation of liver histological alterations, Doppler echography portal flow and measurements of NO and malondialdehyde (MDA); BO/DB (n=13) bile duct occlusion for 20 days followed by biliary drainage by choledochoduodenal anastomosis, 5 days follow-up, same BO group parameters evaluations; group CED (n=4) sham operation and portal flow evaluation trough 20 days; CHB (n=4) sham operation, with hepatic biopsy on 25th day and followed-up trough 25 days, by the same parameters of group BO, with exception of portal flow. Direct bilirubin (DB) and alkaline phosphatase (AP) were evaluated in the group BO, BO/DB and CHB. RESULTS: The bile duct ligation led to an increase of DB and AP, development of liver histological alterations, reduction of portal flow and increase of plasmatic NO and of MDA levels. The bile duct clearing resulted in a reduction of DB, AP, NO, MDA histological alterations and increase of portal flow. CONCLUSION: The biliary occlusion resulted in cholestasis and portal flow reduction, besides the increase of plasmatic NO and of hepatic MDA levels, and histological liver alterations, with a tendency of normalization after the bile duct clearing.

scholarly journals Infection by Gram-Negative Organisms via the Biliary Route Results in Greater Mortality than Portal Venous Infection

2003 ◽  
Vol 10 (4) ◽  
pp. 664-669 ◽  
Author(s):  
D. Rohan Jeyarajah ◽  
Mariusz L. Kielar ◽  
Nicole Frantz ◽  
Guy Lindberg ◽  
Christopher Y. Lu
Keyword(s):  
Bile Duct ◽  
Portal Vein ◽  
Biliary Obstruction ◽  
Bile Duct Ligation ◽  
Lethal Dose ◽  
Bile Duct Obstruction ◽  
Sham Operation ◽  
Duct Obstruction ◽  
E Coli ◽  
Duct Ligation

ABSTRACT Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50% lethal dose (LD50) for E. coli injected into the bile duct was 50 CFU/animal; the LD50 for E. coli injected into the portal vein was 5 × 107 CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.

scholarly journals Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early Cholestasis Assessment

2018 ◽  
Vol 19 (9) ◽  
pp. 2634 ◽  
Author(s):  
Anna Croce ◽  
Giovanni Bottiroli ◽  
Laura Di Pasqua ◽  
Clarissa Berardo ◽  
Veronica Siciliano ◽  
...  
Keyword(s):  
Bile Duct ◽  
Real Time ◽  
Diagnostic Tool ◽  
Bile Duct Ligation ◽  
Fiber Optic Probe ◽  
Duct Ligation ◽  
Male Wistar Rats ◽  
Optic Probe ◽  
Oxidative Products ◽  
Liver Changes

While it is well established that various factors can impair the production and flow of bile and lead to cholestatic disease in hepatic and extrahepatic sites, an enhanced assessment of the biomarkers of the underlying pathophysiological mechanisms is still needed to improve early diagnosis and therapeutic strategies. Hence, we investigated fluorescing endogenous biomolecules as possible intrinsic biomarkers of molecular and cellular changes in cholestasis. Spectroscopic autofluorescence (AF) analysis was performed using a fiber optic probe (366 nm excitation), under living conditions and in serum, on the livers of male Wistar rats submitted to bile duct ligation (BDL, 24, 48, and 72 h). Biomarkers of liver injury were assayed biochemically. In the serum, AF analysis distinctly detected increased bilirubin at 24 h BDL. A continuous, significant increase in red-fluorescing porphyrin derivatives indicated the subversion of heme metabolism, consistent with an almost twofold increase in the serum iron at 72 h BDL. In the liver, changes in the AF of NAD(P)H and flavins, as well as lipopigments, indicated the impairment of mitochondrial functionality, oxidative stress, and the accumulation of oxidative products. A serum/hepatic AF profile can be thus proposed as a supportive diagnostic tool for the in situ, real-time study of bio-metabolic alterations in bile duct ligation (BDL) in experimental hepatology, with the potential to eventually translate to clinical diagnosis.

scholarly journals Effect of Bile Duct Ligation-induced Liver Dysfunction on Methamphetamine Pharmacokinetics and Locomotor Activity in Rats

2019 ◽  
Vol 22 ◽  
pp. 301-312 ◽  
Author(s):  
Michael D Hambuchen ◽  
Michael D Berquist ◽  
Christy M Simecka ◽  
Mitchell R McGill ◽  
Melinda G Gunnell ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Bile Duct ◽  
Liver Dysfunction ◽  
Hepatic Dysfunction ◽  
Bile Duct Ligation ◽  
Dependent Manner ◽  
Duct Ligation ◽  
Male Wistar Rats ◽  
Experimental Treatments ◽  
Altered Liver

Purpose: Methamphetamine (METH) abuse is associated with hepatic dysfunction related comorbidities such as HIV, hepatitis C, and polysubstance abuse with acetaminophen-containing opioid formulations. We aimed to develop a bile duct ligation (BDL)-induced hepatic dysfunction model for studying both METH and experimental treatments for METH abuse in this comorbidity. Methods: Sham or BDL surgery was performed in male Wistar rats on day 0. Liver function was measured throughout the study. On days 7 and 19, serum pharmacokinetics studies were performed with 1 mg/kg subcutaneous (sc) METH. On day 21, this dose was repeated to determine 2 h post-METH brain concentrations. METH-induced open field behaviors were measured every other day (days 12 - 16) with ascending sc doses (0.3 – 3 mg/kg). Results: BDL transiently increased alanine aminotransferase levels and altered liver structure, which resulted in significantly greater METH serum and brain exposure. In the BDL compared to sham group, there was a longer duration of METH-induced locomotor activity (after 1 and 3 mg/kg) and stereotypy (after 3 mg/kg). Conclusions: In rats, liver dysfunction reduced METH clearance, increased brain METH concentrations, and enhanced METH effects on locomotor activity in a dose dependent manner. In addition, this model could be further developed to simulate the associated hepatic dysfunction of key METH abuse comorbidities for preclinical testing of novel pharmacotherapies for effectiveness and/or toxicity in vulnerable populations.

Plasma Membrane Form of Phosphatidate Phosphohydrolase: A Possible Role in Signal Transduction during Liver Fibrogenesis

1993 ◽  
Vol 85 (3) ◽  
pp. 281-287 ◽  
Author(s):  
Christopher P. Day ◽  
Alastair D. Burt ◽  
Ashley Stj. M. Brown ◽  
Mark K. Bennett ◽  
Desmond J. Farrell ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Liver Disease ◽  
Bile Duct ◽  
Common Bile Duct ◽  
Alcoholic Liver Disease ◽  
Bile Duct Ligation ◽  
Sham Operation ◽  
Common Bile Duct Ligation ◽  
Duct Ligation ◽  
Phosphatidate Phosphohydrolase

1. Several growth factors important in liver regeneration and fibrosis stimulate phospholipase D in plasma membranes via a receptor/G-protein-coupled mechanism resulting in hydrolysis of phosphatidylcholine to phosphatidate. Phosphatidate can be further hydrolysed to diacylglycerol by phosphatidate phosphohydrolase. Phosphatidate and diacylglycerol can act as ‘second-messengers’ and regulation of phosphatidate phosphohydrolase activity could control the balance between them. 2. A form of phosphatidate phosphohydrolase, located in the plasma membrane and insensitive to inhibition by N-ethylmaleimide, has recently been identified that is distinct from the ‘metabolic’ form, which is present in the cytosol and microsomes and is sensitive to N-ethylmaleimide. 3. We have investigated the hypothesis that the balance between regeneration and fibrosis is, in part, determined by the activity of plasma membrane phosphatidate phosphohydrolase through its effect on the phosphatidate/diacylglycerol ratio. N-Ethylmaleimide-insensitive and -sensitive phosphatidate phosphohydrolase activities were measured in three hepatic conditions characterized by regeneration and/or fibrosis: alcoholic liver disease in humans (regeneration and fibrosis) and rat livers after either acute CCl-4-induced injury (regeneration) or common bile duct ligation (fibrosis). 4. In patients with alcoholic liver disease, N-ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was higher in cirrhotic biopsies (5.82±0.3 nmol of Pi min−1 mg−1 of protein, n = 19) than in non-cirrhotic biopsies (2.17 ±0.2, n = 23) or in wedge biopsies from healthy subjects undergoing routine cholecystectomy (2.16 ±0.5, n = 6). N-Ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was unchanged in the 10 days after CCl4 treatment but increased progressively in common bile duct-ligated rats (e.g. day 28: ‘sham’ operation, 1.97 ±0.3, chronic bile duct ligation, 6.91 ±1.24 nmol of Pi min−1 mg−1 of protein). N-Ethylmaleimide-insensitive phosphatidate phosphohydrolase activity correlated closely with the degree of fibrosis in humans and rats. N-Ethylmaleimide-sensitive phosphatidate phosphohydrolase activity was unchanged after CCI4 treatment or common bile duct ligation and was not increased in cirrhotic livers. 5. Plasma membrane N-ethylmaleimide-insensitive phosphatidate phosphohydrolase increases in liver fibrosis but not regeneration. Stimulation of phosphatidate phosphohydrolase activity with its effect on the diacylglycerol/phosphatidate ratio may play a role in transduction of the fibrosis signal.

Impact of bile duct obstruction on hepatic E. coli infection: role of IL-10

2006 ◽  
Vol 291 (1) ◽  
pp. G91-G94 ◽  
Author(s):  
D. Rohan Jeyarajah ◽  
Mariusz L. Kielar ◽  
Hoosein Saboorian ◽  
Prameela Karimi ◽  
Nicole Frantz ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bacterial Growth ◽  
Biliary Obstruction ◽  
Bile Duct Ligation ◽  
Hepatic Clearance ◽  
Hepatic Necrosis ◽  
E Coli ◽  
Protein Levels ◽  
Duct Ligation

Biliary obstruction in the setting of hepatic bacterial infection has great morbidity and mortality. We developed a novel murine model to examine the effect of biliary obstruction on the clearance of hepatic Escherichia coli infection. This model may allow us to test the hypothesis that biliary obstruction itself adversely affects clearance of hepatic infections even if the bacteria are introduced into the liver by a nonbiliary route. We ligated the bile ducts of C57BL/6 mice on days − 1, 0, or + 1, relative to a day 0 portal venous injection of E. coli. We monitored survival, hepatic bacterial growth, pathology, and IL-10 protein levels. The role of IL-10 in this model was further examined using IL-10 knockout mice. Mice with bile duct ligation at day +1 or 0, relative to portal venous infection at day 0, had decreased survival compared with mice with only portal venous infection. The impaired survival was associated with greater hepatic bacterial growth, hepatic necrosis, and increased production of IL-10. Interestingly, the transgenic knockout of IL-10 resulted in impaired survival in mice with bile duct ligation and portal venous infection. Biliary obstruction had a dramatic detrimental effect on hepatic clearance of portal venous E. coli infection. This impaired clearance is associated with increased IL-10 production. However, transgenic knockout of IL-10 increased mortality after hepatic infection.

scholarly journals Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis

2003 ◽  
Vol 58 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Ivete Bedin Prado ◽  
Marília Harumi Higuchi dos Santos ◽  
Fábio Pinatel Lopasso ◽  
Kiyoshi Iriya ◽  
Antonio Atílio Laudanna
Keyword(s):  
Bile Duct ◽  
Experimental Model ◽  
Bile Duct Ligation ◽  
Histological Study ◽  
Biliary Tree ◽  
Sham Operation ◽  
Ischemic Necrosis ◽  
Sham Operation Group ◽  
Visceral Peritoneum ◽  
Duct Ligation

OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining). RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.

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. 

Magnesium protects against bile duct ligation-induced liver injury in male Wistar rats

2015 ◽  
Vol 28 (1) ◽  
pp. 32-45
Author(s):  
Tahereh Eshraghi ◽  
Akram Eidi ◽  
Pejman Mortazavi ◽  
Ahmad Asghari ◽  
Seyyed Mohammad Tavangar
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Wistar Rats ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Male Wistar Rats

scholarly journals Effects of melatonin on liver and lung tissues of animals with bile duct ligation-induced hepatopulmonary syndrome

2021 ◽  
Vol 5 (1) ◽  
pp. 097-105
Author(s):  
Dal Bosco Adriane ◽  
Colares Josieli Raskopf ◽  
Bona Sílvia ◽  
De Andrade Lívia Barboza ◽  
Forgiarini Jr. Luiz Alberto ◽  
...  
Keyword(s):  
Bile Duct ◽  
Wistar Rats ◽  
Histological Analysis ◽  
Bile Duct Ligation ◽  
Hepatopulmonary Syndrome ◽  
Lung Parenchyma ◽  
Antioxidant Effect ◽  
Biliary Cirrhosis ◽  
Duct Ligation ◽  
Male Wistar Rats

The objective was to assess the antioxidant effect of melatonin (MLT) on liver and lung tissues of animals with bile duct ligation (BDL)-induced hepato-pulmonary syndrome (HPS). A model of BDL-induced biliary cirrhosis was used in male Wistar rats. Results suggest that MLT has an antioxidant effect on liver and lung tissues in animals with BDL-induced HPS by higher activity of antioxidant enzymes in the group HPS treated with MLT and the histological analysis of lung parenchyma showing decreased damage in this same group, including other analysis described below.

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