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.

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 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.

Mechanisms responsible for the altered pharmacokinetics of Bosentan: analysis utilizing rats with bile duct ligation-induced liver dysfunction

2009 ◽  
Vol 30 (6) ◽  
pp. 326-333 ◽  
Author(s):  
Isao Horiuchi ◽  
Yun-i Mori ◽  
Masato Taguchi ◽  
Fukiko Ichida ◽  
Toshio Miyawaki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Dysfunction ◽  
Bile Duct Ligation ◽  
Duct Ligation

Effect of bile duct ligation-induced liver dysfunction on methamphetamine pharmacokinetics in male and female rats

2020 ◽  
Vol 215 ◽  
pp. 108190
Author(s):  
Michael D. Berquist ◽  
Mitchell R. McGill ◽  
Anna Mazur ◽  
David L. Findley ◽  
Greg Gorman ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Dysfunction ◽  
Bile Duct Ligation ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Duct Ligation

scholarly journals Carvedilol Attenuates the Progression of Hepatic Fibrosis Induced by Bile Duct Ligation

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaopeng Tian ◽  
Chunhong Zhao ◽  
Jinbo Guo ◽  
Shurui Xie ◽  
Fengrong Yin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Antioxidant Properties ◽  
Dependent Manner ◽  
Sod Activity ◽  
Duct Ligation ◽  
Clinical Benefits

Background.The sympathetic nervous system (SNS) is responsible for hepatic stellate cells (HSCs) activation and the accumulation of collagen that occurs in hepatic fibrogenesis. Carvedilol has been widely used for the complication of hepatic cirrhosis in the clinic. Furthermore, it has powerful antioxidant properties. We assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may further enhance its clinical benefits.Methods.Using a bile duct ligation rat model of hepatic fibrosis, we studied the effects of carvedilol on the fibrosis, collagen deposition, and oxidative stress based on histology, immunohistochemistry, western blot, and RT-PCR analyses.Results.Carvedilol attenuated liver fibrosis, as evidenced by reduced hydroxyproline content and the accumulation of collagen, downregulated TIMP-1 and TIMP-2, and upregulated MMP-13. MMP-2 was an exception, which was decreased after carvedilol treatment for 2 weeks and upregulated after carvedilol treatment for 4 weeks. Carvedilol reduced the activation of HSCs, decreased the induction of collagen, transforming growth factor-β1, and MDA content, and strengthened the SOD activity. The antifibrotic effects were augmented as dosages increased.Conclusions.The study indicates that carvedilol attenuated hepatic fibrosis in a dose-dependent manner. It can decrease collagen accumulation and HSCs activation by the amelioration of oxidative stress.

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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