taurochenodeoxycholic-acid and glycoursodeoxycholic-acid

The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of

Topics: Animals; Bacteroides; Colon; Dextran Sulfate; Disease Models, Animal; Dysbiosis; Feces; Firmicutes; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Mice; Taurine; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

Ursodeoxycholic acid (UDCA) has been shown to be a strong modulator of the apoptotic threshold in both hepatic and nonhepatic cells. 3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, appears to cause apoptotic neuronal cell death in the striatum, reminiscent of the neurochemical and anatomical changes associated with Huntington's disease (HD). This study was undertaken (a) to characterize further the mechanism by which 3-NP induces apoptosis in rat neuronal RN33B cells and (b) to determine if and how the taurine-conjugated UDCA, tauroursodeoxycholic acid (TUDCA), inhibits apoptosis induced by 3-NP. Our results indicate that coincubation of cells with TUDCA and 3-NP was associated with an approximately 80% reduction in apoptosis (p < 0.001), whereas neither taurine nor cyclosporin A, a potent inhibitor of the mitochondrial permeability transition (MPT), inhibited cell death. Moreover, TUDCA, as well as UDCA and its glycine-conjugated form, glycoursodeoxycholic acid, prevented mitochondrial release of cytochrome c (p < 0.001), which probably accounts for the observed inhibition of DEVD-specific caspase activity and poly(ADP-ribose) polymerase cleavage. 3-NP decreased mitochondrial transmembrane potential (p < 0.001) and increased mitochondrial-associated Bax protein levels (p < 0.001). Coincubation with TUDCA was associated with significant inhibition of these mitochondrial membrane alterations (p < 0.01). The results suggest that TUDCA inhibits 3-NP-induced apoptosis via direct inhibition of mitochondrial depolarization and outer membrane disruption, together with modulation of Bax translocation from cytosol to mitochondria. In addition, cell death by 3-NP apparently occurs through pathways that are independent of the MPT.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspases; Cells, Cultured; Cytochrome c Group; Hepatocytes; Huntington Disease; Intracellular Membranes; Mitochondria; Mitochondrial Swelling; Neurons; Nitro Compounds; Permeability; Poly(ADP-ribose) Polymerases; Propionates; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

Ursodeoxycholic acid has been widely used as a therapeutic agent in cholesterol gallstones and liver disease patients, but its mechanism of action is still under investigation.. The protective effect of ursodeoxycholic acid, both free, taurine and glycine conjugated, against hepatotoxic bile acids such as chenodeoxycholic acid and its taurine amidate was studied in bile fistula rats and compared with the cholic and taurocholic acid effect.. Tauroursodeoxycholic acid, glycine ursodeoxycholic acid, ursodeoxycholic acid, taurocholic acid and cholic acid were infused iv over 1 hour (8 micromol/min/kg) together with an equimolar dose of either taurochenodeoxycholic acid or chenodeoxycholc acid. Bile flow, total and individual bile acid and biliary lactate dehydrogenase and alkaline phosphatase enzymes were measured.. Taurochenodeoxycholic acid and chenodeoxycholc acid caused cholestasis and liver damage associated with a decreased bile flow, total and individual bile acids secretion accompanied by a biliary leakage of lactate dehydrogenase and alkaline phosphatase enzymes. Tauroursodeoxycholic acid, glycine ursodeoxycholic acid, ursodeoxycholic acid and taurocholic acid, on the contrary, were choleretic, inducing an opposite effect on biliary parameters. Simultaneous infusion of taurochenodeoxycholic acid and the protective bile acid resulted in a functional and morphological improvement of the above parameters in the following order: glycine ursodeoxycholic acid > tauroursodeoxycholic acid > ursodeoxycholic acid followed by taurocholic acid; cholic acid was ineffective.. The results show the protective effect of glycine ursodeoxycholic acid, ursodeoxycholic acid and tauroursodeoxycholic acid. This may be due to a facilitated transport of the toxic bile acid into bile; conjugation with taurine is less effective than glycine. Finally, the better protective effect of ursodeoxycholic acid and its amidates with respect to cholic acid and its taurine conjugated form seems to be related to their different lipophilicity and micellar forming capacity.

Topics: Alkaline Phosphatase; Animals; Bile Acids and Salts; Carrier Proteins; Chenodeoxycholic Acid; Humans; Hydroxysteroid Dehydrogenases; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Membrane Glycoproteins; Rats; Rats, Sprague-Dawley; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

Topics: Bile; Bile Acids and Salts; Cholecystectomy; Gallbladder; Glycochenodeoxycholic Acid; Glycodeoxycholic Acid; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Micelles; Phospholipids; Taurochenodeoxycholic Acid; Taurocholic Acid; Ursodeoxycholic Acid

Topics: Animals; beta-Alanine; Bile; Bile Acids and Salts; Bilirubin; Glycine; Hyperbilirubinemia; Jaundice; Liver; Male; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Taurine; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

The effects were investigated of the choleretic bile salt glycoursodeoxycholate (G-UDCA) and of the cholestatic bile salt taurochenodeoxycholate (T-CDCA) on changes in perfusate Ca2+, glucose and oxygen and in bile calcium and bile flow induced by the administration of (a) vasopressin, (b) glucagon and (c) glucagon plus vasopressin together to the perfused rat liver [Hamada, Karjalainen, Setchell, Millard & Bygrave (1992) Biochem. J. 281, 387-392]. G-UDCA itself increased the secretion of calcium in the bile several-fold, but its principal effect was to augment each of the above-mentioned metabolic events except glucose and oxygen output; particularly noteworthy was its ability to augment the 'transients' in bile calcium and bile flow seen immediately after the administration of vasopressin with or without glucagon. T-CDCA, by contrast, produced opposite effects and attenuated all of the parameters measured, and in particular the transients in bile calcium and bile flow. The data provide evidence of a strong correlation between calcium fluxes occurring on both the sinusoidal and the bile-canalicular membranes and that all are modifiable by glucagon, Ca(2+)-mobilizing hormones and bile salts.

Topics: Animals; Calcium; Drug Synergism; Gallbladder; Glucagon; Kinetics; Liver; Male; Oxygen Consumption; Perfusion; Rats; Rats, Inbred Strains; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid; Vasopressins

To establish whether the calcium-binding capacities of the bile salts play an essential role in their stimulatory effects on biliary calcium secretion, we compared (1) the effects of tauro- and glycoconjugates of ursodeoxycholate (TUDC-GUDC) and cholate (TC-GC) on biliary calcium in bile fistula rats, and (2) the in vitro calcium-binding capacities of mixed micelles containing the same bile salts. The increase of biliary calcium depended on the infused bile salt in the following order: GUDC greater than GC = TUDC greater than GC). The same order was obtained in vitro, so that there was a linear relationship between the slopes of the [Ca] vs. [bile salts] regression lines in vivo and the binding percentages of the four bile salts. Biliary ionized calcium concentration was almost independent of bile salt concentration. However, hepatic bile was supersaturated with calcium carbonate in the presence of the four bile salts. Our results suggest that biliary calcium concentration increases in relation to the calcium-binding capacity of the various bile acids so that ionized biliary calcium remains in equilibrium with plasma. As a result, bile saturation with calcium is almost completely independent of bile salt secretion.

Topics: Animals; Bile; Bile Acids and Salts; Calcium; Calcium Carbonate; Glycocholic Acid; Male; Rats; Rats, Inbred Strains; Taurochenodeoxycholic Acid; Taurocholic Acid; Ursodeoxycholic Acid

The bile salts of ursodeoxycholic acid, glycoursodeoxycholic acid, tauroursodeoxycholic acid, chenodeoxycholic acid, glycochenodeoxycholic acid, and taurochenodeoxycholic acid were each found to inhibit pepsin proteolytic activity in vitro at various concentrations against the refined substrate n-APDT. The sodium salt of ursodeoxycholic acid was the most potent pepsin inhibitor among those tested.

Topics: Animals; Chenodeoxycholic Acid; Deoxycholic Acid; Dipeptides; Glycochenodeoxycholic Acid; In Vitro Techniques; Pepsin A; Substrate Specificity; Swine; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

We examined the intestinal absorption of ursodeoxycholic acid (UDC), glycoursodeoxycholic acid (GUDC) and tauroursodeoxycholic acid (TUDC) using an everted gut sac technique. UDC was absorbed throughout rat small intestine almost to the same extent. Absorption of both GUDC and TUDC, however, varied between jejunum and ileum. Absorption of these conjugated bile acids in the jejunal segments was less than that of UDC. While, absorption of GUDC and TUDC in the terminal ileum was more efficient than UDC. Although 2,4-dinitrophenol had no effect on the jejunal uptake, ileal uptake of these three bile acids was inhibited by 2,4-dinitrophenol.

Topics: Animals; Biological Transport, Active; Chenodeoxycholic Acid; Deoxycholic Acid; In Vitro Techniques; Intestinal Absorption; Kinetics; Male; Rats; Rats, Inbred Strains; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

Chenodeoxycholic acid (cheno) and ursodeoxycholic acid (urso) dissolve cholesterol gallstones in man. Comparative studies of the absorption of cheno and urso are not available. The absorption of urso and cheno and their glycine and taurine conjugates in jejunum, terminal ileum, and colon of the rat were therefore determined in an open in situ perfusion system. Absorption of unconjugated urso and cheno in jejunum, ileum, and colon was similar. In the jejunum conjugated urso and cheno were absorbed only in minimal amounts. In the ileum glycine-conjugated urso was absorbed to a lower extent than glycine-conjugated cheno (6.5 +/- 0.4 vs. 8.6 +/- 0.6 nmol/cm X h at 25 mumol/l bile acid concentration, p less than 0.05) and taurine-conjugated urso was absorbed less than taurine-conjugated cheno (6.4 +/- 0.5 vs. 8.1 +/- 0.7 nmol/cm X h, p less than 0.05). In the colon glycourso and taurourso were not absorbed, while glycocheno and taurocheno were absorbed in small amounts. The low reabsorption rates of urso conjugates in ileum and colon may contribute to the relatively low urso content in bile during urso treatment.

Topics: Animals; Chenodeoxycholic Acid; Colon; Deoxycholic Acid; Glycochenodeoxycholic Acid; Ileum; Intestinal Absorption; Jejunum; Male; Perfusion; Rats; Rats, Inbred Strains; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

A combined infusion of taurocholate (TC) and glycoursodeoxycholate (GU) resulted in a longer choleretic period and a significantly higher excretion of TC compared with the infusion of TC alone, as has been previously observed for the combined infusion of tauroursodeoxycholate (TU) and TC in the rat. It was concluded that GU is as effective as TU in preventing TC induced cholestasis in this species.

Topics: Animals; Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Deoxycholic Acid; Drug Evaluation, Preclinical; Rats; Secretory Rate; Taurochenodeoxycholic Acid; Taurocholic Acid; Ursodeoxycholic Acid

Topics: Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Deoxycholic Acid; Diffusion; Glycine; Glycochenodeoxycholic Acid; In Vitro Techniques; Kinetics; Solubility; Taurine; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid; Water; X-Ray Diffraction

Separation of the glycine and taurine conjugates of ursodeoxycholic acid from those of lithocholic acid, chenodeoxycholic acid, deoxycholic acid, and cholic acid by thin-layer chromatography is described. Thus, on running a silica gel G plate first in a solvent system of n-butanol-water 20:3 and then in a second solvent system of chloroform-isopropanol-acetic acid-water 30:20:4:1, all the above-mentioned conjugated bile acids are separated from one another. The application of this method to study the change in the biliary bile acid conjugation pattern in ursodeoxycholic acid-fed gallstone patients is described.

Topics: Chenodeoxycholic Acid; Chromatography, Thin Layer; Deoxycholic Acid; Glycine; Glycochenodeoxycholic Acid; Glycocholic Acid; Glycodeoxycholic Acid; Lithocholic Acid; Taurochenodeoxycholic Acid; Taurocholic Acid; Taurodeoxycholic Acid; Taurolithocholic Acid; Ursodeoxycholic Acid