Disease relevance of TAUROLITHOCHOLIC ACID

• Scanning electron microscopy of the rat liver. Studies of the effect of taurolithocholate and other models of cholestasis [1].
• Pathogenesis of lithocholate- and taurolithocholate-induced intrahepatic cholestasis in rats [2].
• Consistent with liver toxicity marker activities, serum and liver levels of bile acids, particularly LCA and taurolithocholic acid, were clearly higher in wild-type mice than in FXR-null mice after 1% LCA supplement [3].
• RESULTS: In vivo pharmacokinetic studies revealed that taurolithocholate (3 micro mol/100 g body weight) diminished by 58% canalicular excretion and increased by 96% plasma reflux of (14)C taurocholate [4].
• Effects of taurolithocholate, a Ca2(+)-mobilizing agent, on cell Ca2(+) in rat hepatocytes, human platelets and neuroblastoma NG108-15 cell line [5].

High impact information on TAUROLITHOCHOLIC ACID

• METHODS: After feeding with TC or TLC (1% for 1-4 weeks), we assessed the following in vivo: (1) ductal proliferation by both morphometry and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and measurement of [3H]thymidine incorporation; and (2) the effect of secretin on bile secretion and bicarbonate secretion in vivo [6].
• Our findings suggest that taurolithocholate affects composition and function of the smooth endoplasmic reticulum, and that its action is not limited to the liver plasma membrane [7].
• To investigate whether other membranes are similarly affected, we studied the effect of taurolithocholate on hepatic heme turnover by means of a new 14CO breath test [7].
• This was substantiated by the finding of a 47% reduction of microsomal cytochrome P450 content 3 h after taurolithocholate administration [7].
• Prolonged administration of taurolithocholate, by contrast, decreased metabolic clearance rate of antipyrine by 48% [7].

Chemical compound and disease context of TAUROLITHOCHOLIC ACID

• Therefore, the effect of taurine-conjugated UDCA (TUDCA) was studied in the experimental model of taurolithocholic acid (TLCA)-induced cholestasis on bile flow, hepatobiliary exocytosis, distribution of PKC isoforms, and density of the apical conjugate export pump, Mrp2, in canalicular membranes [8].
• In contrast, simultaneous infusion of dehydrocholate prevented neither cholestasis nor development of the ultrastructural changes induced by taurolithocholate, which were more striking than those caused by taurolithocholate or 3beta-hydroxy-5-cholenoate alone [9].
• The reliability of these findings and their consequences for the mechanism of taurolithocholate-induced cholestasis are discussed and it is suggested that the incorporation of cholesterol into the canalicular membrane reflects only one aspect of the cholestatic effect of taurolithocholate [10].
• 1,3-Butanediol pretreatment on the cholestasis induced in rats by manganese--bilirubin combination, taurolithocholic acid, or alpha-naphthylisothiocyanate [11].
• A 30-mg/kg bolus of acetaminophen was administered intravenously to rats 2 hr (acute cholestasis) or 20 hr (postcholestasis) after intravenous pretreatment with sodium taurolithocholate, 5 mumol/100 g body weight [12].

Biological context of TAUROLITHOCHOLIC ACID

• Sex differences in hepatic sulfation of taurolithocholate in the rat [13].
• TC and TLC stimulate proliferation of small and large cholangiocytes associated with PKC-dependent up-regulation of ABAT [14].
• Hepatoprotection with tauroursodeoxycholate and beta muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways [15].
• The propensity of bile acids to increase iron-induced lipid peroxidation was related to hydrophobicity of the individual bile acids, with the highest effect observed with taurolithocholic acid, whereas TUDC did not have any influence [16].
• Tauroursodeoxycholate did not inhibit the uptake of taurolithocholate, but increased its transcellular passage and biotransformation [17].

Anatomical context of TAUROLITHOCHOLIC ACID

• Modulation of protein kinase C by taurolithocholic acid in isolated rat hepatocytes [18].
• To determine whether this phenomenon was related to the steroid moiety or the form of conjugation, small doses of radiolabeled lithocholic acid glucuronide, lithocholic acid, taurolithocholic acid and/or lithocholic acid sulfate were administered to rats with ligated bile ducts [19].
• It is suggested that taurolithocholate and lithocholate permeabilize the endoplasmic reticulum to Ca2+ and that the resulting permeabilization of this compartment may be involved in the inhibition of bile secretion in mammalian liver [20].
• Electron microscopy studies showed significant alterations in bile canaliculi microvilli in couplets treated with 100 microM TLC [21].
• TLC induced biliary epithelial cell apoptosis [22].

Associations of TAUROLITHOCHOLIC ACID with other chemical compounds

• In vitro sulfotransferase activity was correlated with in vivo sulfation by measuring the percentage of an infused dose (0.03 micron per 100 g per min) of taurolithocholate, which was excreted in bile as the sulfate [13].
• When lithocholic acid sulfate was given, thin-layer chromatography of urine showed two peaks, which were tentatively identified as tauromurideoxycholic and taurolithocholic acid sulfates [19].
• Hepatocyte viability (trypan blue exclusion) declined to 40% to 50% in incubations with taurochenodeoxycholic acid and taurolithocholic acid, whereas taurocholic acid and tauroursodeoxycholic acid were not toxic [23].
• However, taurolithocholate and lithocholate, unlike the hormone, did not induce a significant accumulation of inositol trisphosphate fraction in isolated hepatocytes [20].
• Preadministration of dibutyryl-cAMP, which counteracts taurolithocholate induced impairment in bile salt secretory function in IRHC, restored Bsep localisation in this model [4].

Gene context of TAUROLITHOCHOLIC ACID

• Inhibition by oestradiol 3,17-disulphate and taurolithocholate 3-sulphate was competitive, suggesting that these compounds are MRP4 substrates [24].
• Transport by vesicles of glycine- and taurine-conjugated bile salts and taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep [25].
• Such vectorial transport was also observed for taurolithocholate sulfate, which is transported by rat oatp1 and Mrp2 [26].
• Estradiol-17beta-d-glucuronide (E(2)17G) and taurolithocholate (TLC) induce acute cholestasis-associated with retrieval of the bile salt export pump (Bsep), which parallels with alteration in transport activity. cAMP stimulates the apically directed vesicular trafficking of transporters, partially preventing these alterations [27].
• We evaluated if TC and TLC induction of ABAT expression was dependent on activation of PKC alpha [14].

Analytical, diagnostic and therapeutic context of TAUROLITHOCHOLIC ACID

• However, the morphological changes observed by electron microscopy after treatment with TLC were not modified by co-treatment with TUDC [21].
• In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine [28].
• Reduced cholestatic potency of taurolithocholate during backward perfusion of the rat liver [29].
• Rats were given intravenous injections of a single dose of sodium taurolithocholate, and an almost total cholestasis appeared after 10 minutes and lasted for 3 hours after the injection; then the choleresis began again and 24 hours after the injection, normal values of bile flow were restored [30].
• In rats, hepatic dysfunction was induced with CCl4, SKF 525-A, taurolithocholic acid and alpha-naphthylisothiocyanate and by acute and chronic surgical ligation of the bile duct [31].

References