scholarly journals Hypercortisolism in patients with cholestasis is associated with disease severity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Verena Theiler-Schwetz ◽  
Hansjörg Schlager ◽  
Barbara Obermayer-Pietsch ◽  
Tatjana Stojakovic ◽  
Günter Fauler ◽  
...  
Keyword(s):  
Bile Acid ◽  
Adrenal Gland ◽  
Bile Acids ◽  
Disease Severity ◽  
Total Serum ◽  
Acth Stimulation ◽  
Serum Bile Acids ◽  
Baseline Cortisol ◽  
Duct Ligation ◽  
Gland Function

Abstract Background Cholestasis might lead to an impairment of adrenal function as suggested by in vitro and in vivo data as well as by clinical findings. Bile acid and adrenal steroid metabolism not only share the receptors farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), but supraphysiological bile acid levels were found to stimulate steroidogenesis independent of FXR and TGR5. Our previous experimental findings revealed that mice fed bile acids or subjected to common bile duct ligation develop hypercortisolemia. We thus aimed to assess adrenal gland function in patients with cholestasis. Methods Adrenal gland function was assessed in 36 patients with cholestasis and in 32 patients without cholestasis by measuring total serum cortisol, adrenocorticotropic hormone (ACTH), as well as the increase of cortisol 20 and 30 min after administration of 1 µg of ACTH. Bile acid levels and bile acid pool composition were determined by high-resolution mass spectrometry. Results Patients with cholestasis per definition had markedly elevated levels of alkaline phosphatase (AP), bilirubin and serum bile acids. Baseline cortisol and maximum cortisol after ACTH stimulation were significantly higher in patients with cholestasis compared to controls. Increase of cortisol after ACTH stimulation and ACTH did not differ. In the cholestasis group, baseline cortisol correlated with bilirubin but not with AP, total serum bile acids and levels of conjugated and unconjugated bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels. Conclusions We find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance.

Evaluation of a Commercial Enzymatic Method for the Determination of Total Serum Bile Acids

1980 ◽  
Vol 17 (6) ◽  
pp. 301-306 ◽  
Author(s):  
Per Tobiasson ◽  
Magnus Källberg
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Reference Range ◽  
Reference Value ◽  
Total Serum ◽  
Enzymatic Method ◽  
Normal Range ◽  
Serum Samples ◽  
Serum Bile Acids

An enzymatic method (Sterognost-3α® Flu, Nyegaard & Co, Oslo, Norway) for the determination of total serum bile acids has been evaluated, and reference values for fasting and postprandial total serum bile acids have been established. Precision was rather low in the lower normal range but satisfactory in the upper reference range and for elevated values. The upper reference value for fasting total serum bile acids was 5·0 μmol/l. Maximal postprandial elevations occurred at varying intervals after a test meal and the upper postprandial reference value was 12 μmol/l. Certain serum samples were also analysed by radioimmunological methods for conjugates of cholic and chenodeoxycholic acids. The values obtained with the enzymatic method correlated satisfactorily with those of the radioimmunoassay methods for most of the serum samples analysed. However, a number of samples with slightly elevated bile acid concentrations, as measured by the comparison radioimmunoassay methods, were found to have normal total serum bile acids when measured by the enzymatic method.

Effect of protein on the determination of total bile acids in serum.

1983 ◽  
Vol 29 (1) ◽  
pp. 171-175 ◽  
Author(s):  
N Q Hanson ◽  
E F Freier
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Hydroxysteroid Dehydrogenase ◽  
Inhibitory Effect ◽  
Normal Serum ◽  
Total Serum ◽  
Enzyme Preparations ◽  
Analytical Recovery ◽  
Fluorescence Light

Abstract We measured total serum bile acids on a fluorescence-light-scattering micro centrifugal analyzer by the direct enzymatic method with 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) and with resazurin as a fluorogenic electron acceptor. We found that serum protein has an inhibitory effect on the measurement of bile acids, but this effect was eliminated by adding bovine serum albumin to the reaction mixture in a final protein concentration (12.2 g/L) that was high compared with that contributed by a normal serum specimen. The assay is a sensitive method that reaches equilibrium in 5 min. The method is microscale (5 microL of sample, 150 microL of working reagent), is easy to perform, and is accurate (analytical recovery = 104.1%) and precise (CV = 11.1 and 5.7% on specimens with bile acid concentrations of 7.6 and 35.4 mumol/L, respectively). Normal values are 1-12 and less than 9 mumol/L on nonfasting and fasting individuals, respectively. Pure 3 alpha-hydroxysteroid dehydrogenase must be used: we found several enzyme preparations that gave falsely high values for bile acid.

Specificity and Cross Reactivity in Bile Acid Radioimmunoassays Serum Bile Acids, Radioimmunoassay

1979 ◽  
Vol 12 (8) ◽  
pp. 927-933 ◽  
Author(s):  
D. G. Sampson ◽  
G. M. Murphy ◽  
L. M. Cross ◽  
D. Catty
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cross Reactivity ◽  
Serum Bile Acids

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.

scholarly journals Bicyclol Alleviates Signs of BDL-Induced Cholestasis by Regulating Bile Acids and Autophagy-Mediated HMGB1/p62/Nrf2 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingwen Zhao ◽  
Maojuan Ran ◽  
Ting Yang ◽  
Liwei Chen ◽  
Peixu Ji ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
High Mobility ◽  
Related Factor ◽  
Nrf2 Pathway ◽  
Hepatocellular Damage ◽  
Molecular Pattern ◽  
Duct Ligation ◽  
Extracellular Release ◽  
Key Steps

Cholestasis is a liver disease characterized by the accumulation of toxic bile salts, bilirubin, and cholesterol, resulting in hepatocellular damage. Recent findings have revealed several key steps of cholestasis liver injury including the toxicity of bile acids and accumulation of proinflammatory mediator. In this study, we investigated the protective effect of bicyclol in cholestasis caused by bile duct ligation (BDL), as well as relevant mechanisms. Bicyclol attenuated liver damage in BDL mice by increasing the levels of hydrophilic bile acid such as α-MCA and β-MCA, regulating bile acid-related pathways and improving histopathological indexes. High-mobility group box 1 (HMGB1) is an extracellular damage-associated molecular pattern molecule which can be used as biomarkers of cells and host defense. Bicyclol treatment decreased extracellular release of HMGB1. In addition, HMGB1 is also involved in regulating autophagy in response to oxidative stress. Bicyclol promoted the lipidation of LC3 (microtubule-associated protein 1 light chain 3)-Ⅱ to activate autophagy. The nuclear factor, E2-related factor 2 (Nrf2) and its antioxidant downstream genes were also activated. Our results indicate that bicyclol is a promising therapeutic strategy for cholestasis by regulating the bile acids and autophagy-mediated HMGB1/p62/Nrf2 pathway.

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