Hyodeoxycholic Acid Research Articles

Steroids in the intestinal tract of rats are affected by dietary-fibre-rich barley-based diets.

The aim of the present study was to investigate the influence of dietary-fibre (DF)-rich barley-based diets on bile acids (BA) and neutral sterols (NS) in the intestinal tract of rats. For this purpose, young male Wistar rats (n 50; ten per group) weighing about 67 g were fed either a barley-free diet (control group) or diets containing 500 g barley meal extrudates/kg or a barley meal-Novelose mixture (groups A-D) for 6 weeks. These barley products contained 7-24 g resistant starch/100 g and 7-12 g (1 --> 3),(1 --> 4)-beta-glucan/100 g. More steroids were transported towards the lower parts of the intestinal tract when higher concentrations of macromolecular DF were present in the diets (P < 0.001). Tauroconjugated and primary BA dominated in the contents of the small intestine. Intense enzymic conversion of BA occurred in the caecum and colon. The fermentation of DF affected indirectly the amount of formed secondary BA. The main BA present in the caecal contents were muricholic acids, hyodeoxycholic acid and cholic acid. The BA spectrum in the colonic contents was different from that in the caecum. A higher concentration of NS appeared in the intestinal contents of the groups fed the barley-based diets than in the controls (P < 0.005). The microbial conversion of cholesterol to coprostanol, cholestanone and coprostanone was influenced by the amount and composition of the DF in the gut. DF in the diet may affect the concentration and spectrum of steroids in the intestinal tract. The results are relevant for the discussion of mechanisms behind the cholesterol-lowering effects of DF.

The cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids in intestinal cell lines IEC-6 and Caco-2

Bile acids, especially those with hydrophobic properties, are known to possess cytotoxicity. However, the mechanisms responsible for the cytotoxicity of bile acids are still under investigation. On the other hand, the hydrophilic bile acid, ursodeoxycholic acid has been reported to exhibit therapeutic effects against cytotoxic hydrophobic bile acids. The aim of the present study was to investigate the cytotoxicity of individual bile acids and combinations of bile acids using the intestinal cell lines IEC-6 and Caco-2 cells. The cytotoxicities of individual bile acids and the effects of various bile acid combinations were evaluated using the MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. The bile acids induced cytotoxic effects depending on their hydrophobicity except for hyodeoxycholic acid. In the study for the effects of combined bile acids, not only ursodeoxycholic acid but other hydrophilic bile salts such as cholic acid and hyocholic acid exhibited cytoprotection against deoxycholic acid-induced cytotoxicity. Moreover, even some hydrophobic bile acids, such as chenodeoxycholic acid also exhibited cytoprotection. It is possible that the cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids under certain conditions. The understanding of the precise mechanism of this phenomenon remains to be determined.

Peroxisome Proliferator-activated Receptor α Induces Hepatic Expression of the Human Bile Acid Glucuronidating UDP-glucuronosyltransferase 2B4 Enzyme

Glucuronidation, a major metabolic pathway for a large variety of endobiotics and xenobiotics, is catalyzed by enzymes belonging to the UDP-glucuronosyltransferase (UGT) family. Among UGT enzymes, UGT2B4 conjugates a large variety of endogenous and exogenous molecules and is considered to be the major bile acid conjugating UGT enzyme in human liver. In the present study, we identify UGT2B4 as a novel target gene of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR alpha), which mediates the hypolipidemic action of fibrates. Incubation of human hepatocytes or hepatoblastoma HepG2 and Huh7 cells with synthetic PPAR alpha agonists, fenofibric acid, or Wy 14643 resulted in an increase of UGT2B4 mRNA levels. Furthermore, treatment of HepG2 cells with Wy 14643 induced the glucuronidation of hyodeoxycholic acid, a specific bile acid UGT2B4 substrate. Analysis of UGT2B mRNA and protein levels in PPAR alpha wild type and null mice revealed that PPAR alpha regulates both basal and fibrate-induced expression of these enzymes in rodents also. Finally, a PPAR response element was identified in the UGT2B4 promoter by site-directed mutagenesis and electromobility shift assays. These results demonstrate that PPAR alpha agonists may control the catabolism of cytotoxic bile acids and reinforce recent data indicating that PPAR alpha, which has been largely implicated in the control of lipid and cholesterol metabolism, is also an important modulator of the metabolism of endobiotics and xenobiotics in human hepatocytes.

1H and 13C NMR signal assignments of carboxyl‐linked glucosides of bile acids

AbstractComplete 1H and 13C resonance assignments were carried out for a new type of carboxyl‐linked glucosides of chenodeoxycholic (3α,7α‐dihydroxy‐5β‐cholan‐24‐oic) and hyodeoxycholic (3α,6α‐dihydroxy‐5β‐cholan‐24‐oic) acids by using several homonuclear (1H–1H) and heteronuclear (1H–13C) 2D NMR techniques. Differences in the 1H and 13C resonances between the α‐ and β‐anomers of the ester glucosides of bile acids were clarified for the first time. A comparison of the 1H and 13C signal shifts induced by β‐D‐glucosidation at the 24‐carboxyl and 3α‐hydroxyl groups in the parent 5β‐cholanoic acid was also made. Copyright © 2003 John Wiley &amp; Sons, Ltd.

Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7

Previous studies have shown that several endogenous compounds, such as bilirubin and certain bile acids, are glucosidated in human liver. In this work, we have identified human UDP-glucuronosyltransferase 2B7 (UGT2B7) as the isoform that catalyzes the glucosidation of hyodeoxycholic acid (HDCA). The glucosidation by UGT2B7 was specific for HDCA and was not observed with the other bile acids examined, lithocholic acid, chenodeoxycholic acid, and ursodeoxycholic acid. The kinetics of HDCA glucuronidation and glucosidation by UGT2B7 were characterized. The K m values for glucuronidation and glucosidation of HDCA were 11.6 and 17.9 μM, respectively, with V max values of 4.15 nmol/min/mg protein for glucuronidation and 3.28 nmol/min/mg for glucosidation. At a fixed concentration of HDCA, the apparent K m for UDP-glucuronic acid was 89 μM with a V max of 3.53 nmol/min/mg. The corresponding parameters for UDP-glucose were 442 μM and 1.98 nmol/min/mg, respectively. UGT2B7 catalyzed the addition of the glucose and glucuronic acid moieties to an hydroxyl group on HDCA and also possessed some capacity to use UDP-xylose as sugar donor. The two polymorphic variants of UGT2B7, UGT2B7 ∗1 and UGT2B7 ∗2 could both glucosidate HDCA. This is the first report that identifies UGT2B7 as the enzyme responsible for the glucosidation of the bile acid, HDCA.

Dietary bile acids inhibit potentially elemental diet-induced small intestinal atrophy in rats.

The mechanism responsible for elemental diet (ED)-induced small intestinal atrophy is still unknown. However, it is possible that bile acids in the gut lumen influence this process. The aim of this study was to evaluate the effects of oral bile acid administration during ED feeding. Specific pathogen-free male Sprague-Dawley rats, 10 weeks old, were fed an ED only, ED plus 0.1% (w/w) hyocholic acid, or ED plus 0.1% (w/w) hyodeoxycholic acid ad libitum for 4 weeks. The control rats were fed standard chow ad libitum for 4 weeks. After 4 weeks, the wet weight and whole length of the small intestine, and the mucosal diamine oxidase (DAO) and alkaline phosphatase (ALP) activities were measured. Microscopic histological observation was also performed. ED feeding induced atrophy and elevations in the mucosal DAO and ALP activities in the small intestine. Hyocholic acid and hyodeoxycholic acid administration both tended to inhibit these alterations. In conclusion, ED feeding induced atrophy and elevations in the mucosal DAO and ALP activities in the small intestine. Oral bile acid administration may prevent this atrophy and the elevations in mucosal DAO and ALP activities, which may lead to new therapeutic strategies in patients managed with ED.

A new route for synthesizing cholesterol analogs with fluorocarbon side chains and their liquid-crystalline aliphatic esters

A new and efficient route has been developed to synthesize 17β-(1-methyl-3-perfluoroalkyl)propyl-3β-androsterol ( 1) in nine steps from hyodeoxycholic acid via selective addition of 1-perfluoroalkyl iodide to 24-norchola-5,22-dien-3β-ol. From ( 1), the first series of steroidal liquid crystalline aliphatic esters (smectic A) with fluorocarbon side chains has been prepared.

Synthesis of Bis Dansyl-Modified β -Cyclodextrin Dimer Linked with Azobenzene and Its Fluorescent Molecular Recognition

Flexible dimeric host, 4,4'-azobenzenediamido-bis-{6-(2-dansyl-aminoethyl)6-deoxy-β-cyclodextrin}(beta; -1), has been synthesized in order to investigate itsfluorescent molecular sensory system transforming photoisomerization. Photoisomerizationof β -1 was performed with photoirradiation by a 500W-Xelamp using a Corning 7-37 filter. Host beta; -1 showed puremonomer fluorescence, exhibiting a decrease in fluorescence intensity on accommodationof the guest, and the extent of fluorescence variation with a guest was employed to displaythe sensing ability of β -1, in which the sensing parameter(Δ I/I0)was used to describe the sensing ability. Host β -1could detect chenodeoxycholic acid, ursodeoxycholic acid and hyodeoxycholic acid withhigh selectively. The behaviors of the appended moieties of β -1during host-guest complexation were studied by induced circular dichroism (ICD) andfluorescence spectra and MM2 energy-minimized structure. The ICD and fluorescenceintensities of β -1 decreased on the addition of a guest.The guest-induced variations in the ICD and fluorescence spectra, and MM2 energy-minimized structure suggested that the dansyl moieties of β -1 worked as a hydrophobic cap when a host-guest complexation occurred.

Complete 1H and 13C resonance assignments of glycosidic conjugates of non‐amidated and amidated bile acids

AbstractComplete 1H and 13C resonance assignments on the basis of 1D and 2D NMR were made for seven naturally occurring variants of the 3α‐, 6α‐ and 7β‐O‐β‐D‐glycosidic conjugates (glucosides, N‐acetylglucosaminides and glucuronides) of non‐amidated and glycine‐ and taurine‐amidated bile acids related to lithocholic, hyodeoxycholic, chenodeoxycholic, ursodeoxycolic, deoxycholic and cholic acids. The 1H and 13C NMR signals serving to characterize each of the glycosidic conjugates of bile acids and the effects of the O‐β‐D‐glucosidation, O‐β‐D‐N‐acetylglucosaminidation and O‐β‐D‐glucuronidation at the 3‐, 6‐ or 7‐position in the 5β‐steroid nucleus on the 1H and 13C resonances were clarified and used in the structural elucidation of these bile acid glycosides. Copyright © 2001 John Wiley &amp; Sons, Ltd.

Hyodeoxycholic acid efficiently suppresses atherosclerosis formation and plasma cholesterol levels in mice

We examined the effect of hyodeoxycholic acid (HDCA) on plasma cholesterol levels and atherosclerosis in mice. In wild-type C57BL/6 mice, feeding increasing amounts of HDCA resulted in i) progressive decrease in dietary cholesterol absorption, ii) increased concentrations of HDCA in the gallbladder bile, iii) decreased liver cholesterol content, iv) increased liver cholesterol synthesis, and v) increased plasma concentrations of HDCA. In C57BL/6 LDL-receptor knockouts (LDLR-KO) the addition of HDCA to chow and a 0.5% cholesterol diet decreased their total plasma cholesterol levels by 21% and 62%, respectively, because of a decrease in VLDL and LDL cholesterol. Turnover studies showed that HDCA has no effect on VLDL removal from plasma. Furthermore, the addition of HDCA to chow- and 0.5% cholesterol-fed LDLR-KO mice decreased the aortic root atherosclerosis lesion area by 50% and 80%, respectively. Finally, we tested the effect of HDCA on intestinal tumor formation. Feeding C57BL/6 ApcMin mice with HDCA did not affect the number of tumors but decreased the tumor volume in these animals. These results suggest that HDCA might have beneficial effects in the treatment of increased plasma cholesterol levels and atherosclerosis. —Sehayek, E., J. G. Ono, E. M. Duncan, A. K. Batta, G. Salen, S. Shefer, L. B. Neguyen, K. Yang, M. Lipkin, and J. L. Breslow. Hyodeoxycholic acid efficiently suppresses atherosclerosis formation and plasma cholesterol levels in mice.

Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial cell lines. IEC-6 and Caco-2 cells.

Bile acids have been shown to exhibit varying degrees of cytotoxicity, depending on their hydrophobic-hydrophilic balance. We have recently reported the strong cytotoxicity of hyodeoxycholic acid (HDCA), and the aim of the present study is to investigate the mechanisms underlying the cytotoxicity of HDCA. The intestinal cell lines IEC-6 and Caco-2 cells were used. The cytotoxicities of various bile acids were evaluated using the MTS assay; their cytolytic effects were measured using the LDH release assay. The induction of apoptosis was determined by the specific figure changes in the cellular cytoplasm and nucleus, including DNA ladder formations. IL-8 synthesis induced by the bile acids was measured using an ELISA assay. The bile acids induced cytotoxic effects, LDH release, IL-8 synthesis and apoptosis, depending on their hydrophobic properties. On the other hand, HDCA induced strong cytotoxicity, apoptosis and IL-8 synthesis but not cytolysis, although HDCA has a hydrophilic nature. In addition, HDCA exerted the strongest effects on dispersing monolayer cells. These results strongly suggest that HDCA induces cytotoxicity through its ability to induce apoptosis rather than its detergent effect.

Primary cultures of human hepatocytes but not HepG2 hepatoblastoma cells are suitable for the study of glycosidic conjugation of bile acids

To define the role of glycosidic conjugation of bile acids in humans, an in vitro model system is desirable. We studied the formation of glycosidic conjugates of bile acids in primary cultures of human hepatocytes, isolated from organ donor liver, and the human hepatoblastoma cell line, HepG2. Cells were incubated with 100 μM bile acids (chenodeoxycholic, CDCA; hyodeoxycholic, HDCA; and isoursodeoxycholic acids, isoUDCA) and 1–2 mM uridine diphosphoglycosides (UDP-glucose, UDP-Glc; UDP-glucuronic acid, UDP-GlcA, and UDP- N-acetylglucosamine, UDP-GlcNAc), and octyl glucoside. Media were analysed by electrospray-/gas chromatography-mass spectrometry and electrospray with collision induced dissociation. Primary cultures of human hepatocytes formed glycosidic bile acid conjugates with UDP-sugars (6α-Glc-HDCA, 6α-GlcA-HDCA, and 7β-GlcNAc-isoUDCA) and octyl glucoside as sugar donors (3α-Glc-CDCA). HDCA was completely metabolised to either Glc-HDCA, a compound yet not found in vivo, or GlcA-HDCA. No glycosidic bile acid conjugate was found in media from experiments with HepG2. Thus, primary cultures of human hepatocytes, but not HepG2, are suitable in vitro systems for the study of glycosidic bile acid conjugation reactions.

Hydrophilic and Hydrophobic Bile Acids Exhibit Different Cytotoxicities Through Cytolysis, Interleukin-8 Synthesis and Apoptosis in the Intestinal Epithelial Cell Lines. IEC-6 and Caco-2 cells

Background: Bile acids have been shown to exhibit varying degrees of cytotoxicity, depending on their hydrophobic-hydrophilic balance. We have recently reported the strong cytotoxicity of hyodeoxycholic acid (HDCA), and the aim of the present study is to investigate the mechanisms underlying the cytotoxicity of HDCA. Methods: The intestinal cell lines IEC-6 and Caco-2 cells were used. The cytotoxicities of various bile acids were evaluated using the MTS assay; their cytolytic effects were measured using the LDH release assay. The induction of apoptosis was determined by the specific figure changes in the cellular cytoplasm and nucleus, including DNA ladder formations. IL-8 synthesis induced by the bile acids was measured using an ELISA assay. Results: The bile acids induced cytotoxic effects, LDH release, IL-8 synthesis and apoptosis, depending on their hydrophobic properties. On the other hand, HDCA induced strong cytotoxicity, apoptosis and IL-8 synthesis but not cytolysis, although HDCA has a hydrophilic nature. In addition, HDCA exerted the strongest effects on dispersing monolayer cells. Conclusions: These results strongly suggest that HDCA induces cytotoxicity through its ability to induce apoptosis rather than its detergent effect.

Comparison between Roesy and 13C NMR Complexation Shifts in Deriving the Geometry of Inclusion Compounds: A Study on the Interaction between Hyodeoxycholic Acid and 2-Hydroxypropyl-β-Cyclodextrin

The formation and geometry of the hyodeoxycholic acid (HDCA)/2-hydroxypropyl-β-cyclodextrin (HPβCD) complex in methanol-d4 solution was determined through a rotating frame nuclear Overhauser (ROESY) experiment. The reported results confirmed those independently and previously obtained though the use of 13C complexation shifts in the same solvent. The 13C approach, which needs shorter experimental times and is currently used in the study of HPβCD/bile acid systems, was then substantiated.

Hypocholesterolemic Effect of Dietary Psyllium in Female Rats

We fed cholesterol-enriched (1% cholesterol and 0.2% cholic acid) semipurified diets containing either 3% cellulose or psyllium to 2 groups of female Wistar rats for a period of 8 weeks. The feeding of the cholesterol-enriched semipurified diets resulted in a progressive increase in plasma cholesterol levels in both groups during the 8 weeks of the experiment. The rats fed psyllium, however, had significantly lower plasma cholesterol concentrations than the animals fed cellulose throughout the experimental period (at 8 weeks, 8.92 ± 4.42 and 16.47 ± 8 mmol/l, respectively, means ± SD, n = 14, p < 0.01). Most of the plasma cholesterol in both groups at the end of the study was located in the very low-density lipoprotein (VLDL) fraction (91%) and differences in total plasma cholesterol concentrations were predominantly reflected in differences in VLDL cholesterol. Plasma triglyceride concentrations were not significantly different between the 2 groups. Liver cholesterol concentrations paralleled the concentrations of plasma cholesterol and were significantly lower (p < 0.001) in the psyllium-fed rats (90.31 ± 13.81 µmol/g liver) than in the cellulose-fed rats (60.49 ± 15.25 µmol/g liver). Substitution of psyllium for cellulose resulted in an increase in the excretion of fecal bile acids by 26%, and this increase was predominantly caused by an increased excretion of β-muricholic acid and the bile acids derived from β-muricholic acid (ω-muricholic acid and hyodeoxycholic acid).

Polymorphic Gene Regulation and Interindividual Variation of UDP-glucuronosyltransferase Activity in Human Small Intestine

UDP-glucuronosyltransferases (UGTs) convert dietary constituents, drugs, and environmental mutagens to inactive hydrophilic glucuronides. Recent studies have shown that the expression of the UGT1 and UGT2 gene families is regulated in a tissue-specific fashion. Human small intestine represents a major site of resorption of dietary constituents and orally administered drugs and plays an important role in extrahepatic UGT directed metabolism. Expression of 13 UGT1A and UGT2B genes coupled with functional and catalytic analyses were studied using 18 small intestinal and 16 hepatic human tissue samples. Hepatic expression of UGT gene transcripts was without interindividual variation. In contrast, a polymorphic expression pattern of all the UGT genes was demonstrated in duodenal, jejunal, and ileal mucosa, with the exception of UGT1A10. To complement these studies, interindividual expression of UGT proteins and catalytic activities were also demonstrated. Hyodeoxycholic acid glucuronidation, catalyzed primarily by UGT2B4 and UGT2B7, showed a 7-fold interindividual variation in small intestinal duodenal samples, in contrast to limited variation in the presence of 4-methylumbelliferone, a substrate glucuronidated by most UGT1A and UGT2B gene products. Linkage of RNA expression patterns to protein abundance were also made with several mono-specific antibodies to the UGTs. These results are in contrast to a total absence of polymorphic variation in gene expression, protein abundance, and catalytic activity in liver. In addition, the small intestine exhibits considerable catalytic activity toward most of the different classes of substrates accepted for glucuronidation by the UGTs, which is supported by immunofluorescence analysis of UGT1A protein in the mucosal cell layer of the small intestine. Thus, tissue-specific and interindividual polymorphic regulation of UGT1A and UGT2B genes in small intestine is identified and implicated as molecular biological determinant contributing to interindividual prehepatic drug and xenobiotic metabolism in humans.

Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen

Background. The pathogenesis of inflammatory bowel disease is still unknown. However, it is possible that faecal bile acids influence the clinical course. Aims. To evaluate the eliminating effects of faecal bile acids by the oral adsorbent on dextran sulphate sodium-induced rat colitis. Methods. Rats were given 3% dextran sulphate sodium aqueous solution for 7 days, with or without concomitant administration of oral adsorbent, or the rats were given dextran sulphate sodium for 7 days, followed with or without oral adsorbent for 5 days. Macroscopic and microscopic examinations of the colons and measurement of faecal bile acids were performed. The cytotoxicity of bile salts on Caco-2 cells was also evaluated. Results. Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis. Oral adsorbent was fairly effective in reducing faecal hyodeoxycholic acid concentration. A positive correlation was found between the size of the ulcer area and the faecal hyodeoxycholic acid concentration. In a cell culture study, cytotoxicity of bile acid was parallel with increasing hydrophobicity of the bile acid. However, hyodeoxycholate exhibited severe cytotoxicity, despite its hydrophilic properties. Conclusions. Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis and tended to promote the recovery process. It is possible that bile acids in the gut lumen influence the progression of dextran sulphate sodium-induced colitis and its repair process.

Bilirubin and bile acids may modulate their own metabolism via regulating uridine diphosphate-glucuronosyltransferase expression in the rat.

Uridine diphosphate (UDP)-glucuronosyltransferase (UGT) is a critical enzyme in the elimination of bilirubin and it also plays a role in the metabolism of bile acids. The aim of this study was to determine whether bilirubin and bile acids could modulate their own metabolism by regulating UGT levels in cultured rat hepatocytes. Incubation of hepatocytes with bilirubin (48 micromol/L) for 24 h significantly increased the mRNA expression of UGT1A1 and UGT1A5, two UGT isoforms responsible for the conjugation of bilirubin. The induction of UGT1A1 and UGT1A5 by bilirubin was concentration and time dependent. Treatment with chenodeoxycholic acid, cholic acid, deoxycholic acid, hyodeoxycholic acid and lithocholic acid at a concentration of 100 micromol/L for 48 h significantly enhanced the mRNA expression of UGT2B1, a UGT isoform responsible for the glucuronidation of bile acids. The UGT2B3 mRNA level was also increased by hyodeoxycholic acid. The regulation of UGT2B1 mRNA by chenodeoxycholic acid and hyodeoxycholic acid was dose and time dependent. Our results suggest that bilirubin and bile acids can induce UGT expression and as a result, these compounds may modulate their own metabolism. Such regulation could play a compensatory role in the pathological increased concentrations of these compounds in some hepatobiliary diseases.

Role of perivenous hepatocytes in taurolithocholate-induced cholestasis in vivo

The magnitude of cholestasis induced by taurolithocholic acid (TLCA) and its relationship with phase I metabolism were analyzed in rats treated with bromobenzene (BZ), a chemical that causes selective necrosis of perivenous (zone 3) hepatocytes. Forty-eight hours after BZ administration (600 mg/Kg bw), a single dose of 20 μmol/Kg bw of TLCA was injected. Bile was collected during 180 min and bile flow and total bile acid excretion rate were determined. Biliary bile acid composition was analyzed by gas–liquid chromatography-mass spectrometry. BZ administration did not affect the development of TLCA-induced cholestasis, but exacerbated the bile acid-induced decrease in bile flow during the period of recovery from cholestasis. Biliary excretion of total bile acids after TLCA injection relative to basal value was not effected by BZ. The analysis of bile acid composition in bile revealed that TLCA was partially converted to hyodeoxycholic and muricholic acids. The cumulative excretion of all exogenous bile acids and their contribution to the composition of the biliary bile acid pool were not substantially affected by zone 3 necrosis, suggesting that synthesis and secretion of hydroxylated derivatives of TLCA were maintained by zone 1 and 2 hepatocytes. The relative content of endogenous bile acids was not affected by BZ during TLCA-induced cholestasis. Thus, it seems unlikely that the exacerbation of the cholestasis in BZ-treated rats is due to different choleretic properties and/or toxicity of the bile acid pool.

Association and Guest-induced Dissociation of a Novel α-Helix Peptide Bearing Pyrene and γ-Cyclodextrin in the Side Chains

Abstract A designed α-helix peptide, γ-PR17, which bears γ-cyclodextrin (γ-CD) and pyrene units, exhibits both monomer and excimer emissions, indicating that γ-PR17 forms an association dimer that could be dissociated upon addition of hyodeoxycholic acid as a guest for γ-CD.