BACKGROUND: Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid in the human body. Its therapeutic effects have been recognized in traditional Chinese medicine since ancient times and continue to be used in contemporary Western medicine. TUDCA is classified as a secondary bile acid and is formed by conjugating ursodeoxycholic acid (UDCA) with taurine. Due to its hepatoprotective properties and ability to promote bile production and flow, UDCA has been approved by the US Food and Drug Administration (FDA) for the treatment of primary biliary cholangitis. TUDCA was originally used in the treatment of liver disease, but according to recent findings of current research, TUDCA has therapeutic potential beyond the hepatobiliary area. PURPOSE: In this paper, we aim to summarize the latest findings on the therapeutic potential of TUDCA in a broader clinical context. New findings show that TUDCA finds use not only in the treatment of hepatic disorders, but also in the treatment of cancer, neurodegenerative and cardiovascular diseases, gastrointestinal dysfunctions and glucose metabolism disorders. Due to its multifunctional effects, TUDCA appears to be a promising substance with the potential to become an important part of modern medicine in the treatment of diverse pathological conditions.

• Klíčová slova
• Neurodegenerative diseases, TUDCA, cancer, endoplasmic reticulum stress, immune function, liver disease, liver diseases, malignancy, metabolic diseases, metabolic disorders, tauroursodeoxycholic acid,
• MeSH
• cholagoga a choleretika terapeutické užití   MeSH
• kyselina taurochenodeoxycholová * terapeutické užití   farmakologie   MeSH
• lidé MeSH
• nádory farmakoterapie   MeSH
• tradiční čínská medicína * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cholagoga a choleretika MeSH
• kyselina taurochenodeoxycholová * MeSH
• ursodoxicoltaurine MeSH Prohlížeč

An 8-week feeding experiment was carries out to explore the impacts of dietary tauroursodeoxycholic acid (TUDCA) on growth and gut integrity in spotted seabass (Lateolabrax maculatus) under heat stress (33 °C). Three hundred fish (2 ± 0.02 g) were allocated to triplicate groups and fed five diets containing graded levels of TUDCA at 0, 10, 20, 30, or 40 mg/kg (designated as Con, T10, T20, T30 and T40 diets). Growth performance was significantly (P < 0.05) enhanced in fish receiving ≥30 mg/kg TUDCA compared to the control group. Progressive increases in intestinal total antioxidant capacity and superoxide dismutase activity, accompanied by decreased malondialdehyde concentration, were observed as TUDCA dose increased. TUDCA application modulated the expression of intestinal antioxidant-related genes, downregulating keap1 and upregulating nrf2. Notably, supplementation with 40 mg/kg TUDCA improved intestinal morphology, as evidenced by increased villus height and number. Furthermore, in the T40 group, a marked downregulation of pro-apoptotic genes (caspase3, caspase8, caspase9, and bax) and reduced immunofluorescence intensity were observed, while the expression of the anti-apoptotic gene bcl was significantly up-regulated. Additionally, the expression of pro-inflammatory genes (il-1β, il-8, and tnf-α) and immunofluorescence intensity were significantly reduced in the T40 group compared to control. In contrast, the expression of anti-inflammatory genes (il-4, il-10, and tgf-β) was markedly upregulated. Furthermore, dietary inclusion of 40 mg/kg TUDCA suppressed the expression of endoplasmic reticulum stress-related genes (grp78, chop, perk, atf6, and ire1) and activated the bile acid receptor gene tgr5 in the intestine. Concurrently, TUDCA treatment enhanced the PI3K-Akt signaling pathway, contributing to the inhibition of apoptosis. The data generated in this study demonstrated that dietary supplementation with 40 mg/kg TUDCA promotes growth, activates the Nrf2-Keap1 and PI3K-AKT signaling pathways, enhances intestinal antioxidant defenses, suppresses inflammation and apoptosis, alleviates endoplasmic reticulum stress, and mitigates the physiological impacts of heat stress in L. maculatus reared at elevated temperatures.

• Klíčová slova
• Apoptosis, Endoplasmic reticulum stress, Growth, Gut health, Lateolabrax maculatus, Tauroursodeoxycholic acid,
• MeSH
• antioxidancia metabolismus   MeSH
• dieta veterinární   MeSH
• krmivo pro zvířata analýza   MeSH
• kyselina taurochenodeoxycholová * aplikace a dávkování   metabolismus   MeSH
• náhodné rozdělení MeSH
• Percoidea * růst a vývoj   imunologie   fyziologie   MeSH
• potravní doplňky analýza   MeSH
• reakce na tepelný šok * účinky léků   MeSH
• střeva účinky léků   MeSH
• vysoká teplota škodlivé účinky   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• kyselina taurochenodeoxycholová * MeSH
• ursodoxicoltaurine MeSH Prohlížeč

BACKGROUND: Dyslipidemia and distorted fatty acid (FA) metabolism are frequent biochemical abnormalities associated with anorexia nervosa (AN). Gut microbiota is supposed to play an important role in the etiopathogenesis of AN. Apart from the digestive function of bile acids (BAs), these compounds have multiple metabolic functions due to the activation of specific receptors. OBJECTIVE/AIMS: The aims of the study were to investigate biochemical measures, including plasma lipids (lipoproteins, respectively), fatty acid (FA) patterns, and the profile of plasma Bas, in AN patients and healthy controls (CON). METHODS: Plasma phospholipid FA and BAs profiles were analyzed in 39 women with a restrictive type of AN (AN-R; median age 17 years) and in 35 CON women (median age 20 years). RESULTS: Compared to CON, AN had an increased concentration of HDL-C, increased content of palmitic acid, and decreased proportion of linoleic acid. Moreover, AN had a drop in the level of the sum of PUFAn-6 and increased delta 9 desaturase activity for stearic acid. In AN, we found decreased levels of plasma tauroursodeoxycholic acid (TUDCA). In AN, concentrations of 22:5n-6, 16:0, 20:3n-6 and fat mass index were predic-tors of HDL-C levels (R2 = 0.43). CONCLUSIONS: Patients with AN-R had an increased concentration of HDL-C, decreased levels of total PUFA n-6, and increased activity of D9D for stearic acid. Furthermore, AN exerted decreased levels of TUDCA. Therefore, a decreased level of TUDCA could potentially serve as a marker of AN.

• Klíčová slova
• anorexia nervosa, fatty acid pattern, lipids and lipoproteins, long-chain polyunsaturated fatty acids of n-6 family, multiple linear regression analysis, plasma bile acid composition,
• MeSH
• dospělí MeSH
• dyslipidemie * krev   etiologie   komplikace   MeSH
• kyselina taurochenodeoxycholová * krev   MeSH
• lidé MeSH
• mastné kyseliny * krev   MeSH
• mentální anorexie * krev   komplikace   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• studie případů a kontrol MeSH
• žlučové kyseliny a soli krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina taurochenodeoxycholová * MeSH
• mastné kyseliny * MeSH
• ursodoxicoltaurine MeSH Prohlížeč
• žlučové kyseliny a soli MeSH

Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress; impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.

• Klíčová slova
• ER, Endoplasmic reticulum, Impaired, Receptor, Signaling, Stress, Transmembrane,
• MeSH
• chaperon endoplazmatického retikula BiP MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• receptory buněčného povrchu * metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chaperon endoplazmatického retikula BiP MeSH
• kyselina taurochenodeoxycholová MeSH
• receptory buněčného povrchu * MeSH
• ursodoxicoltaurine MeSH Prohlížeč

BACKGROUND & AIMS: Severity of portal hypertension is usually quantified by measuring the hepatic venous pressure gradient (HVPG). However, due to its invasiveness, alternative markers are being sought. Bile acids (BA), being synthesized, metabolized, and transported by the liver, seem to have the potential to serve as endogenous markers. The aim of the present study was to determine whether serum BA reflect the severity of portal hypertension. METHODS: We correlated serum concentrations of individual BA with portal pressure (as HVPG) in an exploratory cohort of 21 cirrhotic patients with portal hypertension. The predictive potential of selected candidates was then confirmed in an independent validation cohort (n = 214). Additionally, nine previously published noninvasive markers were added to the stepwise logistic regression model to identify the most relevant ones, which were eventually used to create a prognostic index of portal hypertension. RESULTS: Serum levels of taurochenodeoxycholic acid (TCDCA) significantly correlated with HVPG and showed a high potential to predict clinically significant portal hypertension (HVPG ≥ 10 mm Hg: AUROC = 0.97 ± 0.06). This was confirmed in the validation cohort (AUROC = 0.96 ± 0.01). The predictive index (constructed based on AST/ALT, spleen diameter, and TCDCA concentration) was able to distinguish clinically significant portal hypertension with 95% sensitivity and 76% specificity. CONCLUSIONS: TCDCA seems to be a promising noninvasive marker of clinically significant portal hypertension. Its predictive potential may be further enhanced when it is combined with both the AST/ALT ratio and spleen diameter.

• Klíčová slova
• bile acids, cirrhosis, noninvasive markers, portal hypertension, taurochenodeoxycholic acid,
• MeSH
• jaterní cirhóza komplikace   diagnóza   MeSH
• játra MeSH
• kyselina taurochenodeoxycholová * MeSH
• lidé MeSH
• portální hypertenze * diagnóza   MeSH
• portální tlak MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyselina taurochenodeoxycholová * MeSH

The novel copper complex [Cu(phen)2(salubrinal)](ClO4)2 (C0SAL) has been synthesised and characterised. Copper(ii) is coordinated by salubrinal through the thionic group, as shown by the UV-Vis, IR, ESI-MS and tandem mass results, together with the theoretical calculations. The formed complex showed a DPPH radical scavenging ability higher than that of salubrinal alone. Studies on lipid oxidation inhibition showed that the C0SAL concentration, required to inhibit the enzyme, was lower than that of salubrinal. The inhibition of the enzyme could take place via allosteric modulation, as suggested by docking calculations. C0SAL showed a good cytotoxic activity on A2780 cells, 82 fold higher than that of the precursor salubrinal and 1.4 fold higher than that of [Cu(phen)2(H2O)](ClO4)2. Treatment with C0SAL in SKOV3 ovarian cancer cells induced expression of GRP-78 and DDIT3 regulators of ER-stress response. The cytotoxic effect of C0SAL was reverted in the presence of TUDCA, suggesting that C0SAL induces cell death through ER-stress. In A2780 cells treated with C0SAL γ-H2AX was accumulated, suggesting that DNA damage was also involved.

• MeSH
• antivirové látky farmakologie   MeSH
• cinnamáty farmakologie   MeSH
• fenantroliny farmakologie   MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• měď farmakologie   MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• peroxidace lipidů účinky léků   MeSH
• poškození DNA účinky léků   genetika   MeSH
• thiomočovina analogy a deriváty   farmakologie   MeSH
• transkripční faktor CHOP genetika   metabolismus   MeSH
• transmisní elektronová mikroskopie MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,10-phenanthroline MeSH Prohlížeč
• antivirové látky MeSH
• cinnamáty MeSH
• fenantroliny MeSH
• kyselina taurochenodeoxycholová MeSH
• měď MeSH
• salubrinal MeSH Prohlížeč
• thiomočovina MeSH
• transkripční faktor CHOP MeSH
• ursodoxicoltaurine MeSH Prohlížeč

Ovarian surface epithelium (OSE) forms a single layer of mostly cuboidal cells on surface of mammalian ovaries that is inherently exposed to cell stress evoked by tissue damage every ovulation and declines morphologically after menopause. Endoplasmic reticulum (ER) is a principal cell organelle involved in proteosynthesis, but also integrating various stress signals. ER stress evokes a conserved signaling pathway, the unfolded protein response (UPR), leading to cell death or adaptation to stress conditions. In this work, we document that mouse OSE suffers from ER stress during replicative senescence in vitro, develops abnormalities in ER and initiates UPR. Attenuation of ER stress in senescent OSE by tauroursodeoxycholic acid (TUDCA) reconditions ER architecture and leads to delayed onset of senescence. In summary, we show for the first time a mutual molecular link between ER stress response and replicative senescence leading to phenotypic changes of non-malignant ovarian surface epithelium.

• Klíčová slova
• Endoplasmic reticulum stress, Ovarian surface epithelium, Senescence, Tauroursodeoxycholic acid, Unfolded protein response,
• MeSH
• down regulace účinky léků   MeSH
• epitel účinky léků   patologie   ultrastruktura   MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši MeSH
• ovarium patologie   MeSH
• stárnutí buněk účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• tunikamycin farmakologie   MeSH
• upregulace účinky léků   MeSH
• zkracování telomer účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina taurochenodeoxycholová MeSH
• messenger RNA MeSH
• tunikamycin MeSH
• ursodoxicoltaurine MeSH Prohlížeč

Stress of endoplasmic reticulum (ERS) is one of the molecular triggers of adipocyte dysfunction and chronic low inflammation accompanying obesity. ERS can be alleviated by chemical chaperones from the family of bile acids (BAs). Thus, two BAs currently used to treat cholestasis, ursodeoxycholic and tauroursodeoxycholic acid (UDCA and TUDCA), could potentially lessen adverse metabolic effects of obesity. Nevertheless, BAs effects on human adipose cells are mostly unknown. They could regulate gene expression through pathways different from their chaperone function, namely through activation of farnesoid X receptor (FXR) and TGR5, G-coupled receptor. Therefore, this study aimed to analyze effects of UDCA and TUDCA on human preadipocytes and differentiated adipocytes derived from paired samples of two distinct subcutaneous adipose tissue depots, abdominal and gluteal. While TUDCA did not alter proliferation of cells from either depot, UDCA exerted strong anti-proliferative effect. In differentiated adipocytes, acute exposition to neither TUDCA nor UDCA was able to reduce effect of ERS stressor tunicamycin. However, exposure of cells to UDCA during whole differentiation process decreased expression of ERS markers. At the same time however, UDCA profoundly inhibited adipogenic conversion of cells. UDCA abolished expression of PPARγ and lipogenic enzymes already in the early phases of adipogenesis. This anti-adipogenic effect of UDCA was not dependent on FXR or TGR5 activation, but could be related to ability of UDCA to sustain the activation of ERK1/2 previously linked with PPARγ inactivation. Finally, neither BAs did lower expression of chemokines inducible by TLR4 pathway, when UDCA enhanced their expression in gluteal adipocytes. Therefore while TUDCA has neutral effect on human preadipocytes and adipocytes, the therapeutic use of UDCA different from treating cholestatic diseases should be considered with caution because UDCA alters functions of human adipose cells.

• MeSH
• adipogeneze účinky léků   MeSH
• aktivace enzymů účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• cytokiny genetika   MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• kyselina ursodeoxycholová farmakologie   MeSH
• lidé MeSH
• mitogenem aktivovaná proteinkinasa 1 metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 3 metabolismus   MeSH
• podkožní tuk cytologie   MeSH
• proliferace buněk účinky léků   MeSH
• regulace genové exprese účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• tukové buňky cytologie   účinky léků   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• kyselina taurochenodeoxycholová MeSH
• kyselina ursodeoxycholová MeSH
• mitogenem aktivovaná proteinkinasa 1 MeSH
• mitogenem aktivovaná proteinkinasa 3 MeSH
• ursodoxicoltaurine MeSH Prohlížeč

Substances that can affect the crystallization of cholesterol from human bile and consequently the gallstone formation have been given considerable attention. We improved the model system for testing cholesterol crystallization-affecting activity (promoting or inhibiting) of substances and used it for some drugs that are excreted into bile. Besides other factors natural lipid-protein complexes isolated from the native human bile have been shown to be responsible for nucleation and fast crystal growth in cholesterol supersaturated model bile. Artificial lipid-protein complex of taurolithocholate, human serum albumin and Ca2+ (TLTC-HSA-Ca2+) exhibited a lower crystallization activity than both the artificial lipid-protein complexes of taurodeoxycholate, human serum albumin and Ca2+ and the lipid-protein complex isolated from native human bile. The model bile supplemented with this artificial lipid-protein complex (TLTC-HSA-Ca2+) formed a convenient system for testing of various substances (drugs) for their crystallization-affecting activity. From the 20 tested drugs, which could occur at least in small amounts in human bile, the highest crystallization-promoting activity was found for complexes with ampicillin, butorphanol and colchicine. Complexes with tetracycline, thioridazine and doxycycline were the strongest inhibitors. The drugs, which had some effect on cholesterol crystallization, affected somehow the artificial lipid-albumin complex by displacing its components. Interactions of different drugs with HSA and its artificial complexes with the conjugated bile salt and Ca2+ ions were followed by absorption spectroscopy to observe displacement interactions. On the basis of these experiments we could classify drugs into four groups which differ by their effects on spectral characteristics of complexes.

• MeSH
• biologické modely MeSH
• chemické modely MeSH
• cholesterol chemie   MeSH
• krystalizace MeSH
• kyselina taurochenodeoxycholová chemie   MeSH
• kyselina taurodeoxycholová chemie   MeSH
• kyselina taurolithocholová chemie   MeSH
• léčivé přípravky chemie   MeSH
• sérový albumin chemie   MeSH
• vápník chemie   MeSH
• vazba proteinů MeSH
• žluč chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cholesterol MeSH
• kyselina taurochenodeoxycholová MeSH
• kyselina taurodeoxycholová MeSH
• kyselina taurolithocholová MeSH
• léčivé přípravky MeSH
• sérový albumin MeSH
• vápník MeSH

Cholesterol gallstone disease is one of the major health problems in the world. Substances which can affect the crystallisation of cholesterol from human bile have been given considerable attention. Various substances (among them natural lipid-protein complexes) have been tested for cholesterol crystallisation-promoting activity. Various artificial lipid-albumin complexes have been prepared of which taurodeoxycholate-human serum albumin-calcium ions (TDC-HSA-Ca(2+)) had the highest cholesterol crystallisation-promoting activity. This cholesterol crystallisation-promoting activity is similar to that for the lipid-protein complex isolated from native human bile [concanavalin A nonbinding fraction (con A(-) fraction)]. Addition of cholesterol to the TDC-HSA-Ca(2+) complex further increased the cholesterol crystallisation-promoting activity whereas the addition of lecithin had an opposite effect. The interaction of individual components of the TDC-HSA-Ca(2+) complex was followed using several methods. A new effect of Ca(2+) ions (increase in the number of binding sites for bile salts) on the interaction of TDC with HSA was found by equilibrium dialysis. Interaction of TDC with albumin and Ca(2+) did not induce any modification of the secondary structure of albumin. The results of fluorescence spectroscopy may indicate that TDC is at least partially bound to not essentially fatty acid free HSA somehow via admixtures, probably fatty acids. Difference absorption spectrum of the TDC-HSA-Ca(2+)-cholesterol complex was very similar to that of the "natural" lipid-protein complex (con A(-) fraction). From the three drugs with different albumin binding characteristics, only sulphadimethoxin had an observable effect on the cholesterol crystallisation-promoting activity. The action of the TDC-HSA-Ca(2+) complex decreased significantly after the addition of sulphadimethoxin. The addition of TDC modified the absorption spectrum of the sulphadimethoxin-HSA-Ca(2+) complex. It can be suggested that the complex of HSA with bile salts (TDC mainly) and Ca(2+) forms a nucleation centre for cholesterol crystallisation in bile.

• MeSH
• albuminy metabolismus   MeSH
• cholesterol chemie   metabolismus   MeSH
• cirkulární dichroismus MeSH
• fluorescenční spektrometrie MeSH
• krystalizace MeSH
• kyselina taurodeoxycholová analogy a deriváty   MeSH
• lidé MeSH
• vápník metabolismus   MeSH
• žlučové kyseliny a soli metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• albuminy MeSH
• cholesterol MeSH
• kyselina taurodeoxycholová MeSH
• vápník MeSH
• žlučové kyseliny a soli MeSH