scholarly journals Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms

2014 ◽  
Vol 46 (6) ◽  
pp. 527-534 ◽  
Author(s):  
Matthew Quinn ◽  
Matthew McMillin ◽  
Cheryl Galindo ◽  
Gabriel Frampton ◽  
Hae Yong Pae ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Acids ◽  
Blood Brain Barrier ◽  
Bile Duct Ligation ◽  
Brain Barrier ◽  
Blood Brain ◽  
Duct Ligation

Alterations in NADPH oxidase expression and blood–brain barrier in bile duct ligation-treated young rats: Effects of melatonin

2012 ◽  
Vol 60 (8) ◽  
pp. 751-758 ◽  
Author(s):  
Yu-Chieh Chen ◽  
Jiunn-Ming Sheen ◽  
You-Lin Tain ◽  
Chih-Cheng Chen ◽  
Miao-Meng Tiao ◽  
...  
Keyword(s):  
Bile Duct ◽  
Nadph Oxidase ◽  
Blood Brain Barrier ◽  
Bile Duct Ligation ◽  
Brain Barrier ◽  
Young Rats ◽  
Blood Brain ◽  
Duct Ligation

scholarly journals Bile Duct Ligation Upregulates Expression and Function of L-Amino Acid Transporter 1 at Blood–Brain Barrier of Rats via Activation of Aryl Hydrocarbon Receptor by Bilirubin

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1320
Author(s):  
Xiaoke Zheng ◽  
Hanyu Yang ◽  
Lan Qin ◽  
Siqian Wang ◽  
Lei Xie ◽  
...  
Keyword(s):  
Amino Acid ◽  
Bile Duct ◽  
Liver Failure ◽  
Aryl Hydrocarbon Receptor ◽  
Blood Brain Barrier ◽  
Bile Duct Ligation ◽  
Brain Barrier ◽  
Aryl Hydrocarbon ◽  
Duct Ligation ◽  
And Function

Liver failure is associated with increased levels of brain aromatic amino acids (AAAs), whose transport across the blood–brain barrier (BBB) is mainly mediated by L-amino acid transporter 1 (LAT1). We aimed to investigate whether liver failure induced by bile duct ligation (BDL) increases levels of brain AAAs by affecting the expression and function of LAT1. The LAT1 function was assessed using the brain distribution of gabapentin. It was found that BDL significantly increased levels of gabapentin, phenylalanine, and tryptophan in the cortex, hippocampus, and striatum of rats, and upregulated the expression of total LAT1 protein in hippocampus and striatum as well as cortex membrane LAT1 protein. HCMEC/D3 served as in vitro BBB model, and the data showed that both the serum of BDL rats and bilirubin induced LAT1 expression and function, while bilirubin oxidase almost abolished the upregulation of LAT1 protein by bilirubin and the serum of BDL rats. The enhanced function and expression of LAT1 were also observed in the hippocampus and striatum of hyperbilirubinemia rats. Both aryl hydrocarbon receptor (AhR) antagonist α-naphthoflavone and AhR silencing obviously attenuated the upregulation of LAT1 protein by bilirubin or omeprazole. This study provides the first evidence that BDL upregulates LAT1 at the rat BBB, attributed to the activation of AhR by the increased plasma bilirubin. The results highlight the mechanisms causing BDL-increased levels of brain AAAs and their physiological significance.

scholarly journals Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats

1991 ◽  
Vol 280 (2) ◽  
pp. 373-377 ◽  
Author(s):  
S Dueland ◽  
J Reichen ◽  
G T Everson ◽  
R A Davis
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Liver Function ◽  
Urinary Excretion ◽  
Bile Acids ◽  
Bile Duct Ligation ◽  
Microsomal Cytochrome ◽  
Duct Ligation ◽  
Cytochrome P 450

We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.

Increased Serum Bile Acids After Extraheptic Biliary Obstruction Causes Leakiness to the Blood Brain Barrier via the Disruption of Tight Junctions

2011 ◽  
Vol 140 (5) ◽  
pp. S-938
Author(s):  
Matthew Quinn ◽  
Gabriel A. Frampton ◽  
Hae Yong Pae ◽  
Darijana Horvat ◽  
Li Huang ◽  
...  
Keyword(s):  
Bile Acids ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Biliary Obstruction ◽  
Brain Barrier ◽  
Serum Bile Acids ◽  
Blood Brain

scholarly journals Bile acids elicited endothelium-dependent vasoconstrictor hypo-activity through TRPV4 channels in the thoracic aorta of bile duct ligation rats

2019 ◽  
Vol 109 ◽  
pp. 511-518
Author(s):  
Hong-Qian Wang ◽  
Xiao-Yan Meng ◽  
Mo Chen ◽  
Sai-hong Xu ◽  
Mei Zhu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Acids ◽  
Thoracic Aorta ◽  
Bile Duct Ligation ◽  
Duct Ligation

scholarly journals Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury and inflammation from bile duct ligation

2018 ◽  
Vol 314 (3) ◽  
pp. G319-G333 ◽  
Author(s):  
Nadine Gehrke ◽  
Michael Nagel ◽  
Beate K. Straub ◽  
Marcus A. Wörns ◽  
Marcus Schuchmann ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Acids ◽  
Bile Duct Ligation ◽  
Ex Vivo ◽  
Mapk Signaling ◽  
Caspase 8 ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. The aim of the current study was to evaluate the role of the antiapoptotic caspase 8-homolog cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. Transgenic mice exhibiting hepatocyte-specific deletion of cFLIP (cFLIP−/−) were used for in vivo and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL) and the addition of bile acids ex vivo. Loss of cFLIP in hepatocytes promoted acute cholestatic liver injury early after BDL, which was characterized by a rapid release of proinflammatory and chemotactic cytokines (TNF, IL-6, IL-1β, CCL2, CXCL1, and CXCL2), an increased presence of CD68+ macrophages and an influx of neutrophils in the liver, and resulting apoptotic and necrotic hepatocyte cell death. Mechanistically, liver injury in cFLIP−/− mice was aggravated by reactive oxygen species, and sustained activation of the JNK signaling pathway. In parallel, cytoprotective NF-κB p65, A20, and the MAPK p38 were inhibited. Increased injury in cFLIP−/− mice was accompanied by activation of hepatic stellate cells and profibrogenic regulators. The antagonistic caspase 8-homolog cFLIP is a critical regulator of acute, cholestatic liver injury. NEW & NOTEWORTHY The current paper explores the role of a classical modulator of hepatocellular apoptosis in early, cholestatic liver injury. These include activation of NF-κB and MAPK signaling, production of inflammatory cytokines, and recruitment of neutrophils in response to cholestasis. Because these signaling pathways are currently exploited in clinical trials for the treatment of nonalcoholic steatohepatitis and cirrhosis, the current data will help in the development of novel pharmacological options in these indications.

Sign in / Sign up

Export Citation Format

Share Document