Inhibition of Bile Acid and Water Absorption by Phenethylbiguanide in Rat Ileum in vivo

Digestion ◽  
1975 ◽  
Vol 12 (3) ◽  
pp. 179-182 ◽  
Author(s):  
W.F. Caspary ◽  
H. Lücke
Keyword(s):  
Bile Acid ◽  
Water Absorption ◽  
Rat Ileum

Central administration of benzodiazepines alters water absorption by the rat ileum in vivo

1987 ◽  
Vol 93 (2) ◽  
pp. 330-334 ◽  
Author(s):  
R. Fogel ◽  
G. Michelson ◽  
T. Senler ◽  
D. Marshall ◽  
T. Brown ◽  
...  
Keyword(s):  
Water Absorption ◽  
Central Administration ◽  
Rat Ileum

Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid

1997 ◽  
Vol 113 (5) ◽  
pp. 1599-1608 ◽  
Author(s):  
RT Stravitz ◽  
AJ Sanyal ◽  
WM Pandak ◽  
ZR Vlahcevic ◽  
JW Beets ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Messenger Rna ◽  
Rat Ileum ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Acid Transporter

In Vitro Metabolism of E2, G2: Novel Bile Acid-Coupling Camptothecin Analogues, in Rat Liver Microsomes

2021 ◽  
Vol 16 ◽  
Author(s):  
Xiangli Zhang ◽  
Qin Shen ◽  
Yi Wang ◽  
Leilei Zhou ◽  
Qi Weng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Phase I ◽  
Rat Liver ◽  
Deoxycholic Acid ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Rat Liver Microsomes ◽  
Camptothecin Analogues

Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues by introducing deoxycholic acid in 20-position of CPT(camptothecin) with greater anticancer activity and lower systematic toxicity in vivo. Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). Methods: Phase Ⅰ and Phase Ⅱ metabolism of E2 and G2 in rat liver microsomes were performed respectively, and the mixed incubation of phase I and phase Ⅱ metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry. Results: The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some difference. The intrinsic clearance of G2 was 174.7mL/min. mg protein, more than three times of that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations and hydrolysis) and their further glucuronidation products. Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except some difference in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).

Role of amidation in bile acid effect on DNA synthesis by regenerating mouse liver

1995 ◽  
Vol 268 (6) ◽  
pp. G1051-G1059
Author(s):  
E. R. Barbero ◽  
M. C. Herrera ◽  
M. J. Monte ◽  
M. A. Serrano ◽  
J. J. Marin
Keyword(s):  
Bile Acid ◽  
Dna Synthesis ◽  
Bile Acids ◽  
High Performance ◽  
Cell Injury ◽  
Intraperitoneal Administration ◽  
Inhibitory Effect ◽  
Toxicity Tests ◽  
Maximal Effect

Effect of bile acids on DNA synthesis by the regenerating liver was investigated in mice in vivo after partial hepatectomy (PH). Radioactivity incorporation into DNA after [14C]thymidine intraperitoneal administration peaked at 48 h after PH. At this time a significant taurocholate-induced dose-dependent reduction in DNA synthesis without changes in total liver radioactivity content was found (half-maximal effect at approximately 0.1 mumol/g body wt). Effect of taurocholate (0.5 mumol/g body wt) was mimicked by chocolate, ursodeoxycholate, deoxycholate, dehydrocholate, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate. In contrast, chenodeoxycholate, glycocholate, glycochenodeoxycholate, glycoursodeoxycholate, glycodeoxycholate, 5 beta-cholestane, bromosulfophthalein, and free taurine lacked this effect. No relationship between hydrophobic-hydrophilic balance and inhibitory effect was observed. Analysis by high-performance liquid chromatography indicated that inhibition of thymidine incorporation into DNA was not accompanied by an accumulation of phosphorylated DNA precursors in the liver but rather by a parallel increase in nucleotide catabolism. Bile acid-induced modifications in DNA synthesis were observed in vivo even in the absence of changes in toxicity tests, which suggests that the inhibitory effect shared by most unconjugated and tauroconjugated bile acids but not by glycoconjugated bile acids should be accounted for by mechanisms other than nonselective liver cell injury.

scholarly journals Preparation and characteristics of gelatin sponges crosslinked by microbial transglutaminase

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3665 ◽  
Author(s):  
Haiyan Long ◽  
Kunlong Ma ◽  
Zhenghua Xiao ◽  
Xiaomei Ren ◽  
Gang Yang
Keyword(s):  
Cell Proliferation ◽  
Water Absorption ◽  
Crosslinking Agent ◽  
Microbial Transglutaminase ◽  
High Porosity ◽  
Cell Compatibility ◽  
High Viability ◽  
Good Biocompatibility ◽  
The Stability

Microbial transglutaminase (mTG) was used as a crosslinking agent in the preparation of gelatin sponges. The physical properties of the materials were evaluated by measuring their material porosity, water absorption, and elastic modulus. The stability of the sponges were assessed via hydrolysis and enzymolysis. To study the material degradation in vivo, subcutaneous implantations of sponges were performed on rats for 1–3 months, and the implanted sponges were analyzed. To evaluate the cell compatibility of the mTG crosslinked gelatin sponges (mTG sponges), adipose-derived stromal stem cells were cultured and inoculated into the scaffold. Cell proliferation and viability were measured using alamarBlue assay and LIVE/DEAD fluorescence staining, respectively. Cell adhesion on the sponges was observed by scanning electron microscopy (SEM). Results show that mTG sponges have uniform pore size, high porosity and water absorption, and good mechanical properties. In subcutaneous implantation, the material was partially degraded in the first month and completely absorbed in the third month. Cell experiments showed evident cell proliferation and high viability. Results also showed that the cells grew vigorously and adhered tightly to the sponge. In conclusion, mTG sponge has good biocompatibility and can be used in tissue engineering and regenerative medicine.

scholarly journals Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Stef De Lombaerde ◽  
Ken Kersemans ◽  
Sara Neyt ◽  
Jeroen Verhoeven ◽  
Christian Vanhove ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Hepatobiliary Transport ◽  
Bile Acid Transporters ◽  
Significant Difference ◽  
The Impact

Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.

scholarly journals Intestinal bile acid sequestration improves glucose control by stimulating hepatic miR-182-5p in type 2 diabetes

2018 ◽  
Vol 315 (5) ◽  
pp. G810-G823 ◽  
Author(s):  
Leslie R. Sedgeman ◽  
Carine Beysen ◽  
Ryan M. Allen ◽  
Marisol A. Ramirez Solano ◽  
Scott M. Turner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acid ◽  
Glycemic Control ◽  
Mediator Complex ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Zdf Rats ◽  
Direct Target

Colesevelam is a bile acid sequestrant approved to treat both hyperlipidemia and type 2 diabetes, but the mechanism for its glucose-lowering effects is not fully understood. The aim of this study was to investigate the role of hepatic microRNAs (miRNAs) as regulators of metabolic disease and to investigate the link between the cholesterol and glucose-lowering effects of colesevelam. To quantify the impact of colesevelam treatment in rodent models of diabetes, metabolic studies were performed in Zucker diabetic fatty (ZDF) rats and db/db mice. Colesevelam treatments significantly decreased plasma glucose levels and increased glycolysis in the absence of changes to insulin levels in ZDF rats and db/db mice. High-throughput sequencing and real-time PCR were used to quantify hepatic miRNA and mRNA changes, and the cholesterol-sensitive miR-96/182/183 cluster was found to be significantly increased in livers from ZDF rats treated with colesevelam compared with vehicle controls. Inhibition of miR-182 in vivo attenuated colesevelam-mediated improvements to glycemic control in db/db mice. Hepatic expression of mediator complex subunit 1 (MED1), a nuclear receptor coactivator, was significantly decreased with colesevelam treatments in db/db mice, and MED1 was experimentally validated to be a direct target of miR-96/182/183 in humans and mice. In summary, these results support that colesevelam likely improves glycemic control through hepatic miR-182–5p, a mechanism that directly links cholesterol and glucose metabolism. NEW & NOTEWORTHY Colesevelam lowers systemic glucose levels in Zucker diabetic fatty rats and db/db mice and increases hepatic levels of the sterol response element binding protein 2-responsive microRNA cluster miR-96/182/183. Inhibition of miR-182 in vivo reverses the glucose-lowering effects of colesevelam in db/db mice. Mediator complex subunit 1 (MED1) is a novel, direct target of the miR-96/182/183 cluster in mice and humans.

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