scholarly journals Psychiatric Comorbidities and Liver Injury Are Associated With Unbalanced Plasma Bile Acid Profile During Methamphetamine Withdrawal

2022 ◽  
Vol 12 ◽  
Author(s):  
Yuru Ma ◽  
Hongjin Wu ◽  
Huawei Wang ◽  
Fengrong Chen ◽  
Zhenrong Xie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Psychiatric Symptoms ◽  
Lithocholic Acid ◽  
Plasma Concentrations ◽  
Alanine Transaminase ◽  
Gas Liquid Chromatography ◽  
Psychiatric Comorbidities ◽  
Control Subjects ◽  
Liver Functions

BackgroundThe pathogenesis of methamphetamine usedisorders (MUDs) remains largely unknown; however, bile acids may play arole as potential mediators of liver injury and psychiatric comorbidities.The aim of this study was to characterize bile acid (BA) profiles in plasmaof patients with MUDs undergoing withdrawal.MethodsLiver functions and psychiatric symptoms wereevaluated in a retrospective cohort (30 MUDs versus 30 control subjects) andan exploratory cohort (30 MUDs including 10 subjects each at the 7-day,3-month, and 12-month withdrawal stages versus 10 control subjects). BAcompositions in plasma samples from MUD patients in the exploratory cohortwere determined by gas-liquid chromatography.ResultsBoth psychiatric comorbidities andmethamphetamine-induced liver injury were observed in patients in both MUDcohorts. The plasma concentrations of the total BA, cholic acid (CA), andchenodeoxycholic acid (CDCA) were lower in MUD patients relative tocontrols. The maximum decline was observed at the 3-month stage, withgradual recovery at the 12-month stage. Notably, the ratios of deoxycholicacid (DCA)/CA and lithocholic acid (LCA)/CDCA were statistically significantat the 3-month stage comparing with controls. Significant correlations werefound between the LCA/CDCA and taurolithocholic acid (TLCA)/CDCA ratios andthe levels of alanine transaminase and aspartate aminotransferase, andbetween the LCA/CDCA ratio and the HAM-A score.ConclusionBA profile during METH withdrawal weremarkedly altered, with these unbalanced BAs being associated with liverinjury. The associations between BA profiles and psychiatric symptomssuggest an association between specific BAs and disease progression,possibly through the liver-brain axis.

scholarly journals Obeticholic Acid Protects Against Cholestatic Liver Injury Induced by Lithocholic Acid via Inhibiting Exogenous Cell Apoptosis

2021 ◽  
Author(s):  
Yangping Zhu ◽  
Changling Wang ◽  
Jingyi Yu ◽  
Yingying Miao ◽  
Yuanyuan Chai ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Lithocholic Acid ◽  
Farnesoid X Receptor ◽  
Multi Drug Resistance ◽  
Caspase 8 ◽  
Obeticholic Acid ◽  
Cholestatic Liver Injury

Abstract Background: Lithocholic acid (LCA) is one kind of endogenous bile acids which is a typical index in primary biliary cholangitis (PBC). It could cause severe cholestatic liver injury in rodents. Obeticholic acid (OCA) is a major treatment for PBC. However, its effect and mechanism in LCA-induced liver injury was still unclear beside of bile acid regulation. This study aims to evaluate the hepatoprotective effect and mechanism of OCA against LCA-induced cholestatic liver injury. Results: LCA-induced upregulations of ALT, AST, ALP and TBA were reduced and the bile acid profiles in serum, liver and bile were improved significantly by OCA. This bile acid regulating effect of OCA was mainly based on increasing the expression of bile acid efflux transporters bile salt export pump (BSEP), multidrug resistant associated protein 2 (MRP2), MRP3 and multi-drug resistance 3 (MDR3) instead of bile acid synthesis inhibition. Furthermore, it was found that OCA reduced the activation and expression of Caspase 8/3 signaling pathway without the change of p-MLKL and BAX in LCA-induced cholestatic model. And the inhibition of Caspase 8/3 signaling pathway depended on the activation of Farnesoid X receptor (FXR) to inhibit Caspase 8 cleavage to form a active complex.Conclusions: This study found OCA improved LCA-induced cholestatic liver injury via FXR-induced exogenous cell apoptosis, which provided a new evidence for the application of OCA to ameliorate PBC in clinical.

scholarly journals TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury

2012 ◽  
Vol 53 (12) ◽  
pp. 2698-2707 ◽  
Author(s):  
Tsutomu Matsubara ◽  
Naoki Tanaka ◽  
Misako Sato ◽  
Dong Wook Kang ◽  
Kristopher W. Krausz ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Lithocholic Acid ◽  
Phospholipid Metabolism ◽  
Hepatic Bile

scholarly journals Constitutive Androstane Receptor-Mediated Changes in Bile Acid Composition Contributes to Hepatoprotection from Lithocholic Acid-Induced Liver Injury in Mice

2009 ◽  
Vol 37 (5) ◽  
pp. 1035-1045 ◽  
Author(s):  
Lisa D. Beilke ◽  
Lauren M. Aleksunes ◽  
Ricky D. Holland ◽  
David G. Besselsen ◽  
Rick D. Beger ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Acid Composition ◽  
Lithocholic Acid ◽  
Constitutive Androstane Receptor

Pharmacological effects of secondary bile acid microparticles in diabetic murine model

2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Blood Glucose ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Diabetes Treatment ◽  
Secondary Bile Acid ◽  
Glucose Levels ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

scholarly journals Atorvastatin Modulates Bile Acid Homeostasis in Mice with Diet-Induced Nonalcoholic Steatohepatitis

2021 ◽  
Vol 22 (12) ◽  
pp. 6468
Author(s):  
Hana Lastuvkova ◽  
Fatemeh Alaei Faradonbeh ◽  
Jolana Schreiberova ◽  
Milos Hroch ◽  
Jaroslav Mokry ◽  
...  
Keyword(s):  
Bile Acid ◽  
Nonalcoholic Steatohepatitis ◽  
Plasma Concentrations ◽  
Liver Steatosis ◽  
Saturated Fat ◽  
Cardiovascular Complications ◽  
Biliary Secretion ◽  
Fecal Excretion ◽  
High Cholesterol Diet ◽  
Chow Diet

Bile acids (BA) play a significant role in the pathophysiology of nonalcoholic steatohepatitis (NASH). The present study evaluates the modulation of bile acid metabolomics by atorvastatin, a cholesterol-lowering agent commonly used to treat cardiovascular complications accompanying NASH. NASH was induced in mice by 24 weeks of consuming a high–saturated fat, high-fructose, and high-cholesterol diet (F), with atorvastatin administered orally (20 mg/kg/day) during the last three weeks. Biochemical and histological analyses confirmed the effectiveness of the F diet in inducing NASH. Untreated NASH animals had significantly reduced biliary secretion of BA and increased fecal excretion of BA via decreased apical sodium-dependent bile salt transporter (Asbt)-mediated reabsorption. Atorvastatin decreased liver steatosis and inflammation in NASH animals consistently with a reduction in crucial lipogenic enzyme stearoyl–coenzyme A (CoA) desaturase-1 and nuclear factor kappa light chain enhancer of activated B-cell pro-inflammatory signaling, respectively. In this group, atorvastatin also uniformly enhanced plasma concentration, biliary secretion and fecal excretion of the secondary BA, deoxycholic acid (DCA). However, in the chow diet–fed animals, atorvastatin decreased plasma concentrations of BA, and reduced BA biliary secretions. These changes stemmed primarily from the increased fecal excretion of BA resulting from the reduced Asbt-mediated BA reabsorption in the ileum and suppression of synthesis in the liver. In conclusion, our results reveal that atorvastatin significantly modulates BA metabolomics by altering their intestinal processing and liver synthesis in control and NASH mice.

Effects of diltiazem on atrioventricular conduction and arterial blood pressure: correlation with plasma drug concentrations

1984 ◽  
Vol 62 (12) ◽  
pp. 1479-1486 ◽  
Author(s):  
Jean-Paul Clozel ◽  
Jacques Billette ◽  
Gilles Caillé ◽  
Pierre Théroux ◽  
Richard Cartier
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Refractory Period ◽  
Plasma Concentrations ◽  
Atrioventricular Conduction ◽  
Gas Liquid Chromatography ◽  
Conduction Time ◽  
Arterial Blood ◽  
Drug Concentrations ◽  
Atrial Conduction Time

Atrial and atrioventricular conduction variables were studied at control and at the end of each of six consecutive 45-min diltiazem administration periods in eight closed chest-anesthetized dogs. Diltiazem was given as a bolus (50 μg/kg, i.v.) followed by an infusion (0.5 μg∙kg−1∙min−1); doses were doubled in subsequent periods. The plasma concentrations, measured by gas–liquid chromatography, ranged from 8 to 1400 ng/mL and correlated strongly with the doses (r = 0.92; p < 0.01). The Wenckebach cycle length, basic conduction time, and functional refractory period of the atrioventricular (AV) node increased proportionally with plasma concentration (respective r = 0.90, 0.89, 0.80; p < 0.01). The minimum mean plasma concentrations affecting these variables significantly were 37, 83, and 175 ng/mL, respectively. Second or third degree AV blocks developed in all dogs for plasma concentrations between 379 and 1400 ng/mL. In four dogs which were given isoproterenol (0.2 μg∙kg−1∙min−1), these blocks disappeared within 1 min. Atrial conduction time and functional refractory period were slightly but significantly shortened by diltiazem with mean plasma concentrations of 175 ng/mL and over. His–Purkinje intervals were not significantly changed by diltiazem. Systolic and diastolic arterial pressures were decreased by diltiazem (r = −0.64, r = −0.79; p < 0.01) starting with a mean plasma concentration of 83 ng/mL. We conclude that AV nodal conduction variables are progressively prolonged with increasing plasma concentrations of diltiazem; plasma concentrations affecting blood pressure and AV nodal variables overlap; and the AV blocks produced by toxic concentrations of diltiazem can be corrected by isoproterenol.

scholarly journals Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Bernadett Tuka ◽  
Aliz Nyári ◽  
Edina Katalin Cseh ◽  
Tamás Körtési ◽  
Dániel Veréb ◽  
...  
Keyword(s):  
Anthranilic Acid ◽  
Clinical Relevance ◽  
Kynurenic Acid ◽  
Picolinic Acid ◽  
Plasma Concentrations ◽  
Episodic Migraine ◽  
Kynurenine Pathway ◽  
Xanthurenic Acid ◽  
Control Subjects ◽  
Healthy Control

Abstract Background Altered glutamatergic neurotransmission and neuropeptide levels play a central role in migraine pathomechanism. Previously, we confirmed that kynurenic acid, an endogenous glutamatergic antagonist, was able to decrease the expression of pituitary adenylate cyclase-activating polypeptide 1–38, a neuropeptide with known migraine-inducing properties. Hence, our aim was to reveal the role of the peripheral kynurenine pathway (KP) in episodic migraineurs. We focused on the complete tryptophan (Trp) catabolism, which comprises the serotonin and melatonin routes in addition to kynurenine metabolites. We investigated the relationship between metabolic alterations and clinical characteristics of migraine patients. Methods Female migraine patients aged between 25 and 50 years (n = 50) and healthy control subjects (n = 34) participated in this study. Blood samples were collected from the cubital veins of subjects (during both the interictal/ictal periods in migraineurs, n = 47/12, respectively). 12 metabolites of Trp pathway were determined by neurochemical measurements (UHPLC-MS/MS). Results Plasma concentrations of the most Trp metabolites were remarkably decreased in the interictal period of migraineurs compared to healthy control subjects, especially in the migraine without aura (MWoA) subgroup: Trp (p < 0.025), L-kynurenine (p < 0.001), kynurenic acid (p < 0.016), anthranilic acid (p < 0.007), picolinic acid (p < 0.03), 5-hydroxy-indoleaceticacid (p < 0.025) and melatonin (p < 0.023). Several metabolites showed a tendency to elevate during the ictal phase, but this was significant only in the cases of anthranilic acid, 5-hydroxy-indoleaceticacid and melatonin in MWoA patients. In the same subgroup, higher interictal kynurenic acid levels were identified in patients whose headache was severe and not related to their menstruation cycle. Negative linear correlation was detected between the interictal levels of xanthurenic acid/melatonin and attack frequency. Positive associations were found between the ictal 3-hydroxykynurenine levels and the beginning of attacks, just as between ictal picolinic acid levels and last attack before ictal sampling. Conclusions Our results suggest that there is a widespread metabolic imbalance in migraineurs, which manifests in a completely depressed peripheral Trp catabolism during the interictal period. It might act as trigger for the migraine attack, contributing to glutamate excess induced neurotoxicity and generalised hyperexcitability. This data can draw attention to the clinical relevance of KP in migraine.

Screening and Validation of Novel Biomarkers for Cadmium‐Induced Liver Injury Based on Targeted Bile Acid Metabolomics1

2021 ◽  
Author(s):  
meng tian ◽  
Jun Yan ◽  
Honglong Zhang ◽  
Yuhui wei ◽  
Mingtong Zhang ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Novel Biomarkers

Fecal Microbiome and Bile Acid Metabolome in Adult Short Bowel Syndrome

2021 ◽  
Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Short Bowel Syndrome ◽  
Lithocholic Acid ◽  
Intestinal Failure ◽  
Patient Specific ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Fecal Microbiome ◽  
Short Bowel

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.

Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis

1991 ◽  
Vol 70 (1) ◽  
pp. 210-215 ◽  
Author(s):  
M. DeLissio ◽  
L. J. Goodyear ◽  
S. Fuller ◽  
E. L. Krawitt ◽  
J. T. Devlin
Keyword(s):  
Hepatic Cirrhosis ◽  
Treadmill Exercise ◽  
Energy Requirement ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Maximal Aerobic Capacity ◽  
Control Subjects ◽  
Fuel Metabolism

We studied whole body and regional fuel metabolism before, during, and after 90 min of treadmill exercise at 50% of maximal aerobic capacity (VO2max) in four subjects with hepatic cirrhosis and in four normal volunteers. Rates of endogenous glucose production (EGP) were measured using D-[6–3H]glucose infusions and fuel oxidation using indirect calorimetry. In the basal state, cirrhotic subjects had similar rates of EGP compared with controls. Forearm release of alanine and lactate was significantly greater in cirrhotic subjects (P less than 0.05), suggesting increased basal rates of gluconeogenesis. During exercise, EGP increased 2- to 2.5-fold in control subjects (P less than 0.01) but did not increase in cirrhotic subjects. Despite lower glucose concentrations in cirrhotic subjects, progressive hypoglycemia did not occur during exercise, probably because cirrhotic subjects demonstrated increased plasma concentrations of fat-derived substrates and derived a greater percentage of total energy requirement from fat oxidation than did controls (P less than 0.05) and because forearm muscle glucose extraction was significantly lower in cirrhotic subjects compared with controls (0.5 vs. 3.6%, respectively; P less than 0.05). During recovery, control subjects demonstrated significant increases in EGP rates compared with both the basal and exercise periods, but cirrhotic subjects showed no increase. In conclusion, cirrhotic subjects failed to demonstrate the normal increase in EGP during and after exercise. Significant hypoglycemia during exercise did not occur, possibly because of the increased availability of fat-derived fuels, which may spare the requirement for circulating glucose as an oxidative fuel for exercising muscle tissues.

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