Action Of Ursodeoxycholic Acid Research Articles

Evaluation of the survival of fish in acid environment under the action of ursodeoxycholic acid

Currently, there is a sufficient amount of data on agricultural activities, including livestock, animal husbandry and fish farming, which can affect the physico-chemical and biological characteristics of freshwater lakes. However, the consequences of infection, contamination by agricultural activities, on the microbial ecosystem have been unclear.Most toxins are hepatotoxic, so the hepatobiliary system is quite common in fish of all species. Depending on the degree of toxicity of the poison, the severity of the manifestation can manifest itself in the form of massive necrosis of hepatocytes with obvious acute liver failure, and in the form of chronic intoxication with a gradual increase in degenerative processes in the liver.To assess the effectiveness of medicinal products for fish, a first test in the laboratory of the toxicity of pharmaceutical substances that are introduced into the reference preparation is necessary. So, because of diseases - hepatoprotectors is ursodeoxycholic acid (UDCA), which can be of two types - synthetic and extraction. Regardless of its nature, the drug has a place in its pharmacokinetic activity in both veterinary medicine and medicine.At the moment, aqua and mariculture has a colossal dose in modern drugs for pharmacocorrection of pathological non-infectious etiology, which have complexity and a universal integral pharmacological response. However, the discovery of the area of discovery of medicinal compositions occurs due to the non-standard habitat of natural resources compared to classical ones.Research in this area involves the use of new methodological approaches to the design of functional pharmaceutical substances.

Ultrastructural characteristics of Cajal interstitial cells of the muscular membrane of the gallbladder wall in an experimental study of mice under the influence of ursodeoxycholic acid

Background. The use of ursodeoxycholic acid drugs in the treatment of diseases of the hepatobiliary system is highly effective. Interstitial cell of Cajal-like cells are involved in the generation and propagation of spontaneous rhythms and, consequently, the excitability of the gallbladder. The purpose of the study was to determine the morphological changes of Interstitial cell of Cajal-like cells of muscle of the gallbladder wall of experimental mice under the action of ursodeoxy-cholic acid. Methods. The experimental study was performed on 30 mice of the BALB / c line. By the method of simple randomization, the experimental animals were divided into 2 groups: experimental (n = 17) - animals that received ursodeoxycholic acid at a dose of 100.0 mg / kg and control (n = 13) - intact (distilled water). The study was performed using a transmission electron microscope PEM-100-01 according to a standard scheme. Results. The muscular wall of the gallbladder of mice contains numerous interstitial cells in the developed endomysium, among which heteromorphic intersti-tial cell of Cajal-like cells (telocytes) were found in both study groups, containing from 2 to 8 processes, often with branches. The elongated bodies of these cells ranged in size from 8 to 30 μm. The nucleus showed signs of moderate activity, the cytoplasm contained a small number of general-purpose organelles, with the exception of numerous dense small mitochOndria and developed agranular endoplasmic reticulum. Characteristic of interstitial cell of Cajal-like cells was the presence of numerous contacts of the processes with the membrane of neighboring leiomyocytes. A significant increase in the number of interstitial cell of Cajal-like cells in the muscular membrane of the bottom and body of the gallbladder was observed after the introduction of ursodeoxycholic acid. The ultrastructural features of their nuclear and cytoplasmic activity did not differ from those of the control group of animals. Conclusion. Thus, ultrastructural analysis of samples of the muscular wall of the gallbladder wall of mice revealed a significant increase in the number of interstitial cell of Cajal-like cells in the muscular membrane of the bottom and body of the gallbladder after the introduction of ursodeoxycholic acid.

Morphological evaluation of the effects of ursodeoxycholic acid on muscular layer of the gallbladder wall of the mice

Background. Significant prevalence and the possibility of transformation into organic pathology determine the relevance of functional disorders of the gallbladder and sphincter of Oddi in children. The proposed hypothesis is that the increased differentiation of fibroblasts into the smooth muscle cells of the gallbladder wall in the experimental model of mice occurs under the influence of ursodeoxycholic acid. Objective: to determine the histo-ultrastructural changes of cells of the muscular wall of the gallbladder wall of experimental mice under the action of ursodeoxycholic acid. Methods. By the method of simple randomization, mice were divided into 2 groups: experimental group (n = 17) - animals that were received ursodeoxycholic acid at a dose of 100.0 mg/kg and control group (n = 13) - intact (distilled water). Gallbladder morphological examination was performed using light and electron microscopy methods. Results. Impact of ursodeoxycholic acid on the gallbladder muscular layer characterized by moderate hypertrophy of the gallbladder smooth muscle myocytes that contain metabolically active pale nuclei and prominent nucleoli. After the ursodeoxycholic acid administration an increase in the content and activity of the elements of the contractile and energy apparatus of leiomyocytes were found. In addition, ursodeoxycholic acid administration led to an increase in the number of caveolae and micropinocytic vesicles near the cell membrane of smooth muscle cells. Analysis of the components of the interstitium of the mice gallbladder muscular layer of the experimental group revealed the nuclear activity of fibroblasts due to the decondensation of chromatin. Also in the experimental group was characterized by the presence of immature collagen fibrils along with normal striated fibers that was a sign of the rearrangement of the endomysium structure. Conclusion. The effect of ursodeoxycholic acid on the muscular membrane of the gallbladder wall of mice of the experimental group is morphologically manifested by signs of moderate hypertrophy of smooth myocytes, activation of their intracellular transport and increased activity of interstitial fibroblasts.

Drug-induced liver injury: from pathogenesis to treatment

The article presents data on classification, pathogenesis, clinical picture, diagnosis and differentiated treatment tactics, as well as practical algorithm for recognizing and preventing the development of drug-induced liver injury. Pathogenesis of drug-induced liver injury is analyzed, mechanisms of drug metabolism are explained, metabolism phases are described. Four main mechanisms of the pathological effect of drugs on the liver are identified: direct toxic effect on hepatocytes; toxic effect of drug metabolites; immunoallergic liver injury; idiosyncrasy. Peculiar attention is paid to the pathogenesis of drug-induced cholestasis. Direct hepatotoxic reactions develop according to the cytolytic (hepatocellular, parenchymal), cholestatic or mixed option. The most commonly diagnosed clinical variant of drug-induced liver injury is drug-induced hepatitis. Five forms of hepatitis induced by the use of pharmacological agents are distinguished: drug-induced hepatitis with an isolated increase in transaminases (anti-TB drugs, methyldopa, amiodarone, statins); acute hepatitis with jaundice; pseudo-surgical form of acute hepatitis: abdominal pain, fever, jaundice, enlarged gall bladder (cytostatics, antidepressants, antiarrhythmic drugs); severe forms of acute hepatitis with liver failure; chronic drug hepatitis. International diagnostic criteria, basic data on morphological liver changes are presented. Action of ursodeoxycholic acid is explained. It has a litholytic, anticholestatic, cytoprotective, immunomodulating, anti-inflammatory, antitoxic, hypocholesterolemic effect, modulates apoptosis, has a differentiated effect on the regeneration of hepatocytes.

Management of autoimmune hepatitis: Focus on pharmacologic treatments beyond corticosteroids.

In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use but it can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers.

Ursodeoxycholic Acid Stimulates CA 2+ Influx and Exerts Antisecretory Actions in Colonic Epithelial Cells

Background Previously, we have shown that ursodeoxycholic acid (UDCA) exerts antisecretory effects In Vitro and thus may represent a novel therapeutic target in treating intestinal disorders associated with diarrhea. These antisecretory effects are mediated by inhibition of basolateral Na+/K+-ATPase pumps and K+ currents, key components of the Clsecretory pathway. Here, we aimed to further elucidate molecular mechanisms underlying the antisecretory actions of UDCA. Methods Clsecretion was measured as changes in short-circuit current (Isc) across voltage-clamped T84 cell monolayers. Intracellular Ca2+ was measured by fluorescence imaging and cAMP using a commercially available assay. Results As previously reported, UDCA inhibited secretory responses to both Ca2+and cAMP-dependent agonists in T84cells. Antisecretory effects of UDCA were very rapid in onset being apparent within 1 minute of addition. Apical addition of TUDCA, the taurine conjugated, membrane-impermeable derivative of UDCA, reduced CCh-induced secretory responses to 60 ± 10.9% of controls, suggesting the bile acid exerts its effects through interactions with the membrane, rather than intracellularly. Even though it did not stimulate secretory responses, UDCA (50 μM) rapidly elevated intracellular levels of Ca2+ (ΔF340/380 = 0.2995 ± 0.04) in T84 cells (n = 12). UDCA also inhibited subsequent Ca2+ mobilization responses to CCh by 63 ± 0.573% compared to controls (n = 10, p < 0.01). Removal of Ca2+ from the extracellular bathing solution abolished UDCA-induced Ca2+ elevations (n = 5, p < 0.01) but had minimal effects on CCh-induced peak Ca2+ responses. UDCA did not alter FSK-induced elevations in intracellular cAMP levels. Conclusion: These data suggest that UDCA elevates intracellular Ca2+ in colonic epithelial cells through an interaction with the cell membrane and stimulation of Ca2+influx. In contrast to the well-described prosecretory actions of Ca2+ released from intracellular stores, influx of extracellular Ca2+ induced by UDCA appears to be antisecretory. These data provide intriguing new insights into the mechanisms by which UDCA exerts antisecretory actions in the colon.

Ursodeoxycholic acid action on the transport function of the small intestine in normal and cystic fibrosis mice.

Ursodeoxycholic acid possesses choleretic and cytoprotective properties and in cystic fibrosis (CF) it is used to treat the hepatobiliary symptoms of the disease. This study investigated the effects of this bile acid on the transport function of the small intestine in normal and CF mice. The effects of ursodeoxycholic acid were monitored as changes in short-circuit current (SCC) in stripped sheets of small intestine from normal (Swiss MF1) and transgenic CF (Cftr(tm2Cam)) mice. In ileal sheets from Swiss MF1 mice, mucosal ursodeoxycholic acid caused a biphasic increase in SCC. The first phase was reduced by lowering the mucosal Na+ concentration, while the second phase was inhibited by (Cl-)-free conditions, serosal furosemide or mucosal diphenylamine-2-carboxylic acid (DPC), suggesting an initial Na+-dependent bile acid absorption followed by a stimulation of electrogenic Cl- secretion. Serosal application of ursodeoxycholic acid to the ileum and mucosal or serosal application to the mid-intestine and jejunum elicited a secretory response only. Secretion was Ca2+-dependent, but did not involve neural mechanisms. Mucosal mast cells, histamine and serotonin (5-HT) were implicated in the secretory response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 mice, but the secretory response to mucosal or serosal application of the bile acid was impaired in CF tissues. In ilea from CF mice the initial absorptive phase of the response to mucosal ursodeoxycholic acid was still observed. It is concluded that ursodeoxycholic acid induces secretion throughout the murine small intestine by a mechanism that involves degranulation of mucosal mast cells. In the ileum Na+-dependent absorption can also be detected. The secretory response is defective in CF intestine, but the absorptive effect is still present.

Cholestatic syndromes

Further insights into the molecular regulation of bile acid transport and metabolism have provided the basis for a better understanding of the pathogenesis of cholestatic liver diseases. Novel insights into the mechanisms of action of ursodeoxycholic acid should advance our understanding of the treatment of cholestatic liver diseases. Mutations of transporter genes can cause hereditary cholestatic syndromes in both infants and adults as well as cholesterol gallstone disease. Important studies have been published on the pathogenesis, clinical features, and treatment of primary biliary cirrhosis, drug-induced cholestasis, and cholestasis of pregnancy.

Hepatoprotective action of Ursodeoxycholic Acid (UDCA) in alcoholic fatty liver

Hepatoprotective action of Ursodeoxycholic Acid (UDCA) in alcoholic fatty liver

Ursodeoxycholic acid inhibits histamine release from rat peritoneal mast cells⋆

Abstract Although the immunomodulatory properties of ursodeoxycholic acid (UDCA) have been well documented, the effects of UDCA on mast cell function are unknown. The aim of the present study was to investigate in vitro the effects of UDCA on histamine release from mast cells induced by a hydrophobic bile acid (i.e. chenodeoxycholic acid) and by classical mast cell activators (i.e. compound 48/80 and concanavalin A). We incubated 5 × 10 5 purified rat peritoneal mast cells with the aforementioned agents in the presence or absence of UDCA and assessed the extent of mast cell activation by quantitating the release of histamine, a prototypic mast cell-derived mediator. UDCA dose-dependently inhibited histamine release from mast cells induced by chenodeoxycholic acid, compound 48/80, and concanavalin A. Our in vitro data suggest a hitherto unrecognized, inhibitory action of UDCA on histamine release from mast cells and a potential benefit of UDCA for mast cell-related disorders.

Ursodeoxycholic acid-dependent activation of the glucocorticoid receptor

Therapeutic effectiveness of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis strongly indicates that UDCA possesses immunomodulatory activities. In order to further investigate mechanical background of such UDCA action, we first asked whether UDCA modulates glucocorticoid-mediated signal transduction. Using electrophoretic mobility-shift assay, we demonstrated that treatment with UDCA promoted the specific complex formation between the cytosol protein and the glucocorticoid-response element DNA in a dose-dependent fashion in vitro, and also nuclear translocation of the glucocorticoid receptor (GR) in vivo. Gene transfer experiments revealed that UDCA induced cellular CAT activities in a GR-dependent fashion, but rather weakly as compared to synthetic glucocorticoid dexamethasone.

Evidence for a direct hepatoprotective action of ursodeoxycholic acid in primary human hepatocytes

Evidence for a direct hepatoprotective action of ursodeoxycholic acid in primary human hepatocytes