Taurochenodeoxycholic acid ameliorates and ursodeoxycholic acid exacerbates small intestinal inflammation

1997 ◽  
Vol 272 (5) ◽  
pp. G1249-G1257 ◽  
Author(s):  
A. Uchida ◽  
T. Yamada ◽  
T. Hayakawa ◽  
M. Hoshino
Keyword(s):  
Bile Acid ◽  
Food Intake ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Intestinal Inflammation ◽  
Myeloperoxidase Activity ◽  
Hydrophobicity Index ◽  
Inflammatory Parameters ◽  
Intestinal Length ◽  
Small Intestinal

Intraluminal bacteria, food intake, and bile play important roles in indomethacin-induced small intestinal inflammation in rats. Tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) inhibit hydrophobic bile acid-induced damage in various types of cells. We investigated the effects of these bile acids along with the possible influence of other bile acids on this model of inflammation. Clinical and intestinal inflammatory parameters and bile secretion were assessed after 7-day dietary bile acid pretreatments and subsequent indomethacin injections. UDCA significantly enhanced indomethacin-associated reductions in food intake and body weight, increases in gross inflammatory scores and myeloperoxidase activity, and the shortening of small intestinal length. Taurochenodeoxycholic acid (TCDCA) significantly normalized the clinical inflammatory parameters, prevented indomethacin-induced increases in the biliary contents of secondary bile acids and hydrophobicity index, and tended to attenuate the intestinal inflammation. Although elevated biliary levels of muricholic acids and a decreased hydrophobicity index were evident before indomethacin injection in the TCDCA case, these alterations could not explain the TCDCA-mediated protection. Dietary TCDCA attenuates whereas UDCA exacerbates intestinal inflammation in this model. Alterations in the bile composition (increases in UDCA and chenodeoxycholic acid) may explain the observed modification effects.

scholarly journals Overview of Bile Acids Signaling and Perspective on the Signal of Ursodeoxycholic Acid, the Most Hydrophilic Bile Acid, in the Heart

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 159 ◽  
Author(s):  
Noorul Izzati Hanafi ◽  
Anis Syamimi Mohamed ◽  
Siti Hamimah Sheikh Abdul Kadir ◽  
Mohd Hafiz Dzarfan Othman
Keyword(s):  
Heart Failure ◽  
Bile Acid ◽  
Chronic Heart Failure ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
G Protein ◽  
Hormone Receptors ◽  
Nuclear Hormone Receptors ◽  
Heart Failure Patients ◽  
G Protein Coupled

Bile acids (BA) are classically known as an important agent in lipid absorption and cholesterol metabolism. Nowadays, their role in glucose regulation and energy homeostasis are widely reported. BAs are involved in various cellular signaling pathways, such as protein kinase cascades, cyclic AMP (cAMP) synthesis, and calcium mobilization. They are ligands for several nuclear hormone receptors, including farnesoid X-receptor (FXR). Recently, BAs have been shown to bind to muscarinic receptor and Takeda G-protein-coupled receptor 5 (TGR5), both G-protein-coupled receptor (GPCR), independent of the nuclear hormone receptors. Moreover, BA signals have also been elucidated in other nonclassical BA pathways, such as sphingosine-1-posphate and BK (large conductance calcium- and voltage activated potassium) channels. Hydrophobic BAs have been proven to affect heart rate and its contraction. Elevated BAs are associated with arrhythmias in adults and fetal heart, and altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile, in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase in serum bile acid concentrations. In contrast, the most hydrophilic BA, known as ursodeoxycholic acid (UDCA), has been found to be beneficial in improving peripheral blood flow in chronic heart failure patients and in protecting the heart against reperfusion injury. This review provides an overview of BA signaling, with the main emphasis on past and present perspectives on UDCA signals in the heart.

scholarly journals Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat

2008 ◽  
Vol 294 (4) ◽  
pp. G1009-G1016 ◽  
Author(s):  
Clavia Ruth Wooton-Kee ◽  
David E. Cohen ◽  
Mary Vore
Keyword(s):  
Bile Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Bile Acids ◽  
Fold Increase ◽  
Bile Acid Pool ◽  
Hydrophobicity Index ◽  
Acid Pool ◽  
Bile Acid Transporters ◽  
Cholic Acids

Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool.

scholarly journals Effect of indomethacin on bile acid-phospholipid interactions: implication for small intestinal injury induced by nonsteroidal anti-inflammatory drugs

2010 ◽  
Vol 298 (5) ◽  
pp. G722-G731 ◽  
Author(s):  
Yong Zhou ◽  
Elizabeth J. Dial ◽  
Rand Doyen ◽  
Lenard M. Lichtenberger
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Surface ◽  
Intestinal Injury ◽  
Disruptive Effect ◽  
Plasma Membrane Permeability ◽  
Small Intestinal Injury ◽  
Inflammatory Drugs ◽  
Small Intestinal ◽  
Anti Inflammatory

The injurious effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the small intestine was not appreciated until the widespread use of capsule endoscopy. Animal studies found that NSAID-induced small intestinal injury depends on the ability of these drugs to be secreted into the bile. Because the individual toxicity of amphiphilic bile acids and NSAIDs directly correlates with their interactions with phospholipid membranes, we propose that the presence of both NSAIDs and bile acids alters their individual physicochemical properties and enhances the disruptive effect on cell membranes and overall cytotoxicity. We utilized in vitro gastric AGS and intestinal IEC-6 cells and found that combinations of bile acid, deoxycholic acid (DC), taurodeoxycholic acid, glycodeoxycholic acid, and the NSAID indomethacin (Indo) significantly increased cell plasma membrane permeability and became more cytotoxic than these agents alone. We confirmed this finding by measuring liposome permeability and intramembrane packing in synthetic model membranes exposed to DC, Indo, or combinations of both agents. By measuring physicochemical parameters, such as fluorescence resonance energy transfer and membrane surface charge, we found that Indo associated with phosphatidylcholine and promoted the molecular aggregation of DC and potential formation of larger and isolated bile acid complexes within either biomembranes or bile acid-lipid mixed micelles, which leads to membrane disruption. In this study, we demonstrated increased cytotoxicity of combinations of bile acid and NSAID and provided a molecular mechanism for the observed toxicity. This mechanism potentially contributes to the NSAID-induced injury in the small bowel.

Probucol-poly(meth)acrylate-bile acid nanoparticles increase IL-10, and primary bile acids in prediabetic mice

2019 ◽  
Vol 10 (9) ◽  
pp. 563-571
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Ryu Takechi ◽  
Hesham Al-Sallami ◽  
Momir Mikov ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Stress Effects ◽  
Acid Accumulation ◽  
Acid Formulation ◽  
Potential Applications ◽  
Regulatory Effects

Aim: Common features in insulin-resistance diabetes include inflammation and liver damage due to bile acid accumulation. Results & methodology: This study aimed to test in vivo pharmacological effects of combining two drugs, ursodeoxycholic acid that has bile acid regulatory effects, and probucol (PB) that has potent anti-oxidative stress effects, using a new poly(meth)acrylate nano-targeting formulation on prediabetic mice. Mice were made diabetic and were fed daily with either PB, nanoencapsulated PB or nanoencapsulated PB-ursodeoxycholic acid before blood, tissues, urine and feces were collected for inflammation and bile acid measurements. The nanoencapsulated PB-ursodeoxycholic acid formulation increased plasma IL-10, and increased the concentration of primary bile acids in the liver and heart. Conclusion: Results suggest potential applications in regulating IL-10 in insulin-resistance prediabetes.

scholarly journals Ursodeoxycholic acid increases low-density lipoprotein binding, uptake and degradation in isolated hamster hepatocytes

1991 ◽  
Vol 280 (3) ◽  
pp. 589-598 ◽  
Author(s):  
B Bouscarel ◽  
H Fromm ◽  
S Ceryak ◽  
M M Cassidy
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Direct Effect ◽  
Specific Binding ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Maximum Effect ◽  
Low Density ◽  
Ldl Binding

Ursodeoxycholic acid (UDCA), in contrast to both chenodeoxycholic acid (CDCA), its 7 alpha-epimer, and lithocholic acid, enhanced receptor-dependent low-density lipoprotein (LDL) uptake and degradation in isolated hamster hepatocytes. The increase in cell-associated LDL was time- and concentration-dependent, with a maximum effect observed at approx. 60 min with 1 mM-UDCA. This increase was not associated with a detergent effect of UDCA, as no significant modifications were observed either in the cellular release of lactate dehydrogenase or in Trypan Blue exclusion. The effect of UDCA was not due to a modification of the LDL particle, but rather was receptor-related. UDCA (1 mM) maximally increased the number of 125I-LDL-binding sites (Bmax.) by 35%, from 176 to 240 ng/mg of protein, without a significant modification of the binding affinity. Furthermore, following proteolytic degradation of the LDL receptor with Pronase, specific LDL binding decreased to the level of non-specific binding, and the effect of UDCA was abolished. Conversely, the trihydroxy 7 beta-hydroxy bile acid ursocholic acid and its 7 alpha-epimer, cholic acid, induced a significant decrease in LDL binding by approx. 15%. The C23 analogue of UDCA (nor-UDCA) and CDCA did not affect LDL binding. On the other hand, UDCA conjugated with either glycine (GUDCA) or taurine (TUDCA), increased LDL binding to the same extent as did the free bile acid. The half maximum time (t1/2) to reach the full effect was 1-2 min for UDCA and TUDCA, while GUDCA had a much slower t1/2 of 8.3 min. Ketoconazole (50 microM), an antifungal agent, increased LDL binding, but this effect was not additive when tested in the presence of 0.7 mM-UDCA. The results of the studies indicate that, in isolated hamster hepatocytes, the UDCA-induced increase in receptor-dependent LDL binding and uptake represents a direct effect of this bile acid. The action of the bile acid is closely related to its specific structural conformation, since UDCA and its conjugates are the only bile acids shown to express this ability thus far. However, certain agents other than bile acids, such as ketoconazole, have a similar effect. Finally, the studies suggest that the recruitment of LDL receptors from a latent pool in the hepatocellular membrane may be the mechanism by which UDCA exerts its direct effect.

scholarly journals Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Huan Zhang ◽  
Huanji Xu ◽  
Chenliang Zhang ◽  
Qiulin Tang ◽  
Feng Bi
Keyword(s):  
Colorectal Cancer ◽  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Inhibitory Effect ◽  
Bile Acid Metabolism ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rhoa Activity ◽  
Relationship Of

AbstractThe Hippo/YAP pathway plays an important role in the development of cancers. Previous studies have reported that bile acids can activate YAP (Yes Associated Protein) to promote tumorigenesis and tumor progression. Ursodeoxycholic acid (UDCA) is a long-established old drug used for cholestasis treatment. So far, the effect of UDCA on YAP signaling in colorectal cancer (CRC) is not well defined. This study means to explore relationship of UDCA and YAP in CRC. UDCA suppressed YAP signaling by activating the membrane G-protein-coupled bile acid receptor (TGR5). TGR5 mainly regulated cAMP/PKA signaling pathway to inhibit RhoA activity, thereby suppressing YAP signaling. Moreover, the restoration of YAP expression alleviated the inhibitory effect of UDCA on CRC cell proliferation. In AOM/DSS-induced CRC model, UDCA inhibited tumor growth in a concentration-dependent manner and decreased expression of YAP and Ki67. UDCA plays a distinguished role in regulating YAP signaling and CRC growth from the primary bile acids and partial secondary bile acids, demonstrating the importance of maintaining normal intestinal bile acid metabolism in cancer patients. It also presents a potential therapeutic intervention for CRC.

scholarly journals Su1880 – Secondary Bile Acids Protect Against Intestinal Inflammation Via Bile Acid Tgr5 Receptor

2019 ◽  
Vol 156 (6) ◽  
pp. S-647
Author(s):  
Sidhartha R. Sinha ◽  
Yeneneh Haileselassie ◽  
Linh Nguyen ◽  
carolina tropini ◽  
Laren S. Becker ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intestinal Inflammation ◽  
Secondary Bile Acids

Fucose Ameliorate Intestinal Inflammation Through Modulating the Crosstalk Between Bile Acids and Gut Microbiota in a Chronic Colitis Murine Model

2020 ◽  
Vol 26 (6) ◽  
pp. 863-873 ◽  
Author(s):  
Jun Ke ◽  
Ying Li ◽  
Chaoqun Han ◽  
Ruohang He ◽  
Rong Lin ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Murine Model ◽  
Intestinal Inflammation ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Chronic Colitis ◽  
16S Rna ◽  
Bile Acid Profiles

Abstract Background Recurrent intestinal inflammation is frequently associated with aberrant bile acid profiles and microbial community. Fucose exerts a protective effect on commensal bacteria in the case of intestinal pathogen infection. We speculated that fucose might also have certain impact on the microbial ecosystem under the chronic colitis setting. Methods To validate our hypothesis, multi-omics examination was performed in combination with microbiomics and metabonomics in a chronic dextran sulfate sodium (DSS) murine model in the presence or absence of fucose. The 16S RNA sequencing was carried out to determine the ileum and colon microbiota. Primary and secondary bile acids, together with the respective taurine and glycine conjugates, were quantified through ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS). Moreover, enzymes involved in regulating bile acid synthesis were also detected. Finally, an experiment was carried out on the antibiotic-treated mice to examine the role of gut microbiota. Results Administration of exogenous-free fucose markedly alleviated the inflammatory response in colitis mice. In addition, excessive intestinal bile acid accumulated in DSS mice was decreased in the presence of fucose, along with the restoration of the compromised regulation on hepatic bile acid synthesis. Moreover, the shifts in bile acid profiles were linked with the improved gut microbiome dysbiosis. However, the protective effects of fucose were abolished in mice treated with antibiotic cocktail, indicating that microbiota played a pivotal role. Conclusions Findings in this study suggest that fucose ameliorates colitis through restoring the crosstalk between bile acid and gut microbiota.

scholarly journals Differential Effects of Sulfur Amino Acid-Restricted and Low-Calorie Diets on Gut Microbiome Profile and Bile Acid Composition in Male C57BL6/J Mice

2020 ◽  
Author(s):  
Sailendra N Nichenametla ◽  
Dwight A L Mattocks ◽  
Vishal Midya ◽  
Jelena Shneyder
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Food Intake ◽  
Bile Acids ◽  
Acid Composition ◽  
Gut Microbiome ◽  
Sulfur Amino Acid ◽  
Low Calorie ◽  
Microbiome Profile ◽  
Body Weights

Abstract Diet can affect health and longevity by altering the gut microbiome profile. Sulfur amino acid restriction (SAAR), like caloric restriction, extends lifespan. But, its effect on the gut microbiome profile and functional significance of such effects are understudied. We investigated whether SAAR alters the gut microbiome profile and bile acid composition, an index of microbial metabolism. We also compared these changes with those induced by a 12% low-calorie diet (LCD). Male 21-week-old C57BL6/J mice were fed control (CD; 0.86% methionine), SAAR (0.12% methionine), and LCD diets (0.86% methionine). After 10 weeks on the diet, plasma markers and fecal microbial profiles were determined. SAAR mice had lower body weights and IGF-1, and higher food intake and FGF-21 than CD mice. Compared to SAAR mice, LCD mice had higher body weights, and lower FGF-21 and food intake, but similar IGF-1. β-Diversity indices were different between SAAR and LCD, and LCD and CD, but not between CD and SAAR. In groupwise comparisons of individual taxa, differences were more discernable between SAAR and LCD than between other groups. Abundances of Firmicutes, Clostridiaceae, and Turicibacteraceae were higher, but Verrucomicrobia was lower in SAAR than in LCD. Secondary bile acids and the ratio of secondary to primary bile acids were lower in SAAR than in LCD. SAAR favored bile acid conjugation with glycine at the expense of taurine. Overall, SAAR and LCD diets induced distinct changes in the gut microbiome and bile acid profiles. Additional studies on the role of these changes in improving health and lifespan are warranted.

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