Disease relevance of Taurochenodeoxycholate

• Infusion of taurochenodeoxycholate (0.22 mumol/min/gm liver) did not produce cholestasis and did not reduce the biliary excretion of bile acids in the Eisai hyperbilirubinemic rats [1].
• The addition of tauroursodeoxycholate to taurochenodeoxycholate or taurodeoxycholate led to time-dependent and concentration-dependent reduction or elimination of the toxicity of the more hydrophobic component [2].
• Pure synthetic conjugates of a trihydroxy bile acid, taurocholate, and three dihydroxy bile acids, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate were used to completely solubilize [14C]cholesterol and polar lipids for steady rate intraduodenal infusion for 8 hr in bile fistula rats [3].
• Enzymatic and molecular cytochemistry was used to detect and follow the hepatotoxic effects caused in overnight-fasted Sprague-Dawley rats by a 1-h continuous intrafemoral infusion of taurochenodeoxycholate at 0.4 and 0.8 mumol-1 min-1 100 g-1 body weight dose levels [4].
• Furthermore, the quantitative relationship between taurocholate and taurochenodeoxycholate in cirrhosis was reversed from that in acute hepatitis [5].

High impact information on Taurochenodeoxycholate

• However, when PI-3K was inhibited with wortmannin or dominant-negative PI 3-K, TCDC-induced Bid-GFP mitochondrial translocation and cytochrome c release [6].
• In this study, the mechanisms by which the TCDC/PI 3-K survival signal disrupts Fas signaling were examined [6].
• Mucin secretion was stimulated by extracellular adenosine 5'-triphosphate via P2U receptors, cytosolic calcium increase, and PKC and by taurochenodeoxycholate via cytosolic calcium increase and Ca2+/CaM-kinase II [7].
• Purified kinesin transported microtubules in vitro with a velocity of approximately 0.5 microns/s; this activity was significantly inhibited by 0.5-1 mmol/L taurochenodeoxycholate but not by tauroursodeoxycholate [8].
• In-vivo replenishment of the bile salt pool by intravenous infusion of either taurocholate or taurochenodeoxycholate (1 mumol/min) completely prevented the pigmentary precipitation [9].

Chemical compound and disease context of Taurochenodeoxycholate

• Taurine conjugate of ursodeoxycholate plays a major role in the hepatoprotective effect against cholestasis induced by taurochenodeoxycholate in rats [10].

Biological context of Taurochenodeoxycholate

• Tauroursodeoxycholate and tauro-beta-muricholate exert cytoprotection by reducing intrahepatocyte taurochenodeoxycholate content [11].
• Protein kinase C down-regulation caused a 70% reduction in TUDC-induced mucin secretion, but did not affect TCDC-induced secretion, which was mediated predominantly by Ca(2+)/calmodulin-dependent protein kinase II activation [12].
• The effect of sulfate esterification of the 3 alpha- or 7 alpha-hydroxyl groups of taurochenodeoxycholate on calcium binding was studied at 0.154 M NaCl in the presence and absence of phosphatidylcholine using a calcium electrode [13].
• The results indicate that increased calcium binding due to the presence of phosphatidylcholine in bile salt solutions depends, in part, on the hydrophilicity of the bile salt and that the interaction of monosulfate esters of taurochenodeoxycholate with phosphatidylcholine leads to the formation of a high affinity calcium binding site [13].
• Increased fecal bile acid excretion and alterations of the circulating bile acid pool by removal of dihydroxy bile acids (e.g., taurochenodeoxycholate) appear to be main modulators of the hypocholesterolemic action of PSY by leading to an up-regulation of hepatic bile acid synthesis [14].

Anatomical context of Taurochenodeoxycholate

• Taurochenodeoxycholate was more toxic to erythrocytes than taurodeoxycholate; the two were equally toxic to rat hepatocytes [2].
• TCDC stimulated Cl(-) efflux and mucin secretion in cultured cells, and both effects were sodium-dependent [12].
• These results reveal that taurolithocholate, taurochenodeoxycholate and glycochenodeoxycholate and ursodeoxycholate inhibit P-glycoprotein-mediated drug transport function in multidrug resistant cell lines and in canalicular membrane vesicles [15].
• Vasopressin reduces taurochenodeoxycholate-induced hepatotoxicity by lowering the hepatocyte taurochenodeoxycholate content [16].
• Effect of taurochenodeoxycholate or tauroursodeoxycholate upon biliary output of phospholipids and plasma-membrane enzymes, and the extent of cell damage, in isolated perfused rat livers [17].

Associations of Taurochenodeoxycholate with other chemical compounds

• Brains were perfused in situ with a Ringer solution for 5 min followed by a 1 min perfusion containing either sodium deoxycholate (DOC), taurochenodeoxycholate (TCDC), or Ringer/DNP [18].
• Cholate and taurochenodeoxycholate, however, were ineffective inhibitors of transferase YcYc at all values of pH [19].
• DEAE-Sephadex sequestered only 49% of the taurocholate and 84% of the taurochenodeoxycholate, but completely removed all of the phospholipid and cholesterol from micelles containing either bile salt [20].
• Also the primary dihydroxy bile salt, chenodeoxycholate, in its deconjugated form caused moderate damage to the mucosa, whereas its conjugated form, taurochenodeoxycholate, had no effect [21].
• The solubilizing powers of taurocholate, taurochenodeoxycholate and tauroursodeoxycholate for monoolein and cholesterol, and the size of the bile salt-monoolein-cholesterol micelles have been determined [22].

Gene context of Taurochenodeoxycholate

• Taurochenodeoxycholate, a conjugated bile acid, also caused dose-dependent induction of COX-2 but higher concentrations of bile acid (200-1200 micro M) were required [23].
• Immortalized mouse cholangiocytes were incubated with taurocholate, taurochenodeoxycholate, glycochenodeoxycholate (GCDC), taurodeoxycholate, and tauroursodeoxycholate (TUDC), followed by flow-cytometric analysis and caspase activity assay to evaluate the induction of apoptosis [24].
• Deoxycholate, chenodeoxycholate, taurochenodeoxycholate and glycochenodeoxycholate also inhibited cholera-toxin-induced HGF production at non-cytotoxic doses [25].
• Taurochenodeoxycholate is transported with the highest affinity and is the most potent inducer of ATPase activity [26].
• For each of these compounds, OATP-mediated uptake was cis-inhibited by the OATP substrate taurochenodeoxycholate and the transport activities correlated well with the amounts of cRNA injected [27].

Analytical, diagnostic and therapeutic context of Taurochenodeoxycholate

• Thin layer and high performance liquid chromatography identified the 3-monosulfate ester as the predominant product of in vitro enzymatic sulfation of glyco- and taurochenodeoxycholate by rat liver and kidney and hamster liver [28].
• Taurochenodeoxycholate 7-sulphate in human urine was unequivocally identified on the basis of behaviour in HPLC using mobile phases of different pH values [29].
• Treatment of experimentally induced cerebral atherothromboembolism in an animal model with streptokinase and taurochenodeoxycholate [30].

References