Disease relevance of TAUROCHENODEOXYCHOLIC ACID

• Taurohyodeoxycholic acid protects against taurochenodeoxycholic acid-induced cholestasis in the rat [1].
• To clarify a possible pathogenic role for bile salts in the hyperdynamic circulation of cirrhosis, we studied the vasoactive effects of three different bile salts-tauroursodeoxycholic acid, taurochenodeoxycholic acid and taurodeoxycholic acid-in cirrhotic rats [2].
• Cytoprotection by tauroursodeoxycholic acid and tauro-beta-muricholic acid against taurochenodeoxycholic acid-induced toxicity was examined with reference to intracellular bile acid content in primary cultured rat hepatocytes [3].
• The objective of this study was to determine whether urso- (UDC), cheno- (CDC), and taurochenodeoxycholic acid (TCDC) exert a pro- or antiinflammatory action in the acute and chronic phase of the indomethacin model of a long lasting ileitis in rats [4].

High impact information on TAUROCHENODEOXYCHOLIC ACID

• Vitamin E reduces oxidant injury to mitochondria and the hepatotoxicity of taurochenodeoxycholic acid in the rat [5].
• Furthermore, primary cultures of rat hepatocytes were exposed to glycochenodeoxycholic acid (GCDCA), tauroursodeoxycholic acid, taurochenodeoxycholic acid, and to cytokines [6].
• In contrast to taurochenodeoxycholic acid and tauroursodeoxycholic acid, GCDCA induced apoptosis in a Fas-associated protein with death domain-independent pathway in hepatocytes [6].
• Cloning and expression of a pig liver taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21): a novel member of the CYP4A subfamily [7].
• A cytochrome P450 expressed in pig liver was cloned by polymerase chain reaction using oligonucleotide primers based on amino acid sequences of the purified taurochenodeoxycholic acid 6alpha-hydroxylase [7].

Chemical compound and disease context of TAUROCHENODEOXYCHOLIC ACID

• RESULTS: Taurochenodeoxycholic acid and chenodeoxycholc acid caused cholestasis and liver damage associated with a decreased bile flow, total and individual bile acids secretion accompanied by a biliary leakage of lactate dehydrogenase and alkaline phosphatase enzymes [8].

Biological context of TAUROCHENODEOXYCHOLIC ACID

• Transfection of the cDNA for CYP4A21 into COS cells resulted in the synthesis of an enzyme that was recognized by antibodies raised against the purified pig liver enzyme and catalyzed 6alpha-hydroxylation of taurochenodeoxycholic acid [7].
• Both the extent of hydroxylation and the state of conjugation of the bile acids had marked effects on the induction of the enzyme, and the order of the enzyme induction was conjugated cholic acid much greater than cholic acid greater than taurochenodeoxycholic acid greater than or equal to chenodeoxycholic acid [9].
• Inhibition of phagocytosis by taurochenodeoxycholic acid or taurodeoxycholic acid was essentially dose dependent [10].
• To assess the effects of bile acids, we investigated the cell proliferation and collagen formation of primary cultured Ito cells that were incubated with a Kupffer cell conditioned medium (KCCM) treated with either taurochenodeoxycholic acid (TCDCA) or tauroursodeoxycholic acid (TUDCA) in short-term (8 h) or long-term (48 h) cultures [11].
• Substrate saturation kinetics were performed using the 18-fold purified enzyme and the lowest Km values were obtained for 3alpha,7alpha-dihydroxy bile acid and bile salt substrates including chenodeoxycholic acid (Km 0.048 mM), glycochenodeoxycholic acid (Km 0.083 mM) and taurochenodeoxycholic acid (Km 0.059 mM) [12].

Anatomical context of TAUROCHENODEOXYCHOLIC ACID

• The properties of the species-specific 6 alpha-hydroxylation of taurochenodeoxycholic acid were studied in subcellular fractions from pig liver [13].
• However, transport studies, which were carried out by using purified plasma membrane vesicles derived from the fetal-facing pole of the human trophoblast, revealed that [14C]taurocholate transport was affected by both another bile acid (taurochenodeoxycholic acid) and a non-bile acid cholephilic organic anion (bromosulfophthalein) [14].
• Characterisation of taurochenodeoxycholic acid 6 alpha-hydroxylase from pig liver microsomes [15].
• Tauroursodeoxycholic acid is less damaging than taurochenodeoxycholic acid to the gastric and esophageal mucosa [16].
• The gallstone diet decreased the concentration of bile acids in gallbladder bile, but greatly increased the percentage of taurochenodeoxycholic acid, whereas psyllium preferentially decreased all taurine-conjugated bile acid levels and expanded glycocholate output [17].

Associations of TAUROCHENODEOXYCHOLIC ACID with other chemical compounds

• We evaluated the effect of idebenone, a coenzyme Q analogue, on taurochenodeoxycholic acid (TCDC)-induced cell injury and oxidant stress in isolated rat hepatocytes and on glycochenodeoxycholic acid (GCDC)-induced generation of hydroperoxides in fresh hepatic mitochondria [18].
• We therefore investigated the influence of vasopressin on the hepatotoxicity and biliary excretion of taurochenodeoxycholic acid in primary cultured rat hepatocytes and isolated perfused rat liver models [19].
• The binding in vitro of the sodium salts of cholic acid, chenodeoxycholic acid, deoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, and glycodeoxycholic acid by alfalfa, bran, cellulose, lignin, and cholestyramine was measured [20].
• 4. Exogenous taurochenodeoxycholic acid was metabolised to tauromuricholic acid by isolated hepatocytes [21].
• A fraction of cytochrome P-450 catalysing an efficient 6 alpha-hydroxylation of taurine-conjugated 3 alpha,7 alpha-dihydroxy-5 beta- cholanoic acid (taurochenodeoxycholic acid) was partially purified from pig liver microsomes [15].

Gene context of TAUROCHENODEOXYCHOLIC ACID

• The Vmax for 6alpha-hydroxylation of taurochenodeoxycholic acid by CYP3A4 was 18.2 nmol/nmol P450/min and the apparent Km was 90 microM [22].
• BACKGROUND/AIMS: We examined taurochenodeoxycholic acid-induced hepatotoxicity with reference to Ca2+ and calpain involvement, intracellular bile acid content, and zone specificity in isolated perfused rat liver [23].
• Troleandomycin, a selective inhibitor of CYP3A enzymes, inhibited 6alpha-hydroxylation of taurochenodeoxycholic acid almost completely at a 10 microM concentration [22].
• Gene structure of pig sterol 12alpha-hydroxylase (CYP8B1) and expression in fetal liver: comparison with expression of taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21) [24].
• METHODOLOGY: Taurochenodeoxycholic acid or chenodeoxycholic acid was infused into the portal vein and lactate dehydrogenase release, a marker of hepatocyte injury, in the effluent and bile acid output were measured in the presence and absence of either nickel, a membranous Ca2+ channel blocker, or calpain inhibitor in isolated perfused rat liver [23].

Analytical, diagnostic and therapeutic context of TAUROCHENODEOXYCHOLIC ACID

• In fed animals, the concentration of the biliary taurochenodeoxycholic acid increased above the control values 5 and 35 min after the intravenous injections of NT [25].
• HPLC analysis showed a trend towards increased per cent tauroconjugation of all individual bile salts, with a significant rise in taurochenodeoxycholic acid (from 15.0 +/- 9.4% to 25.3 +/- 9.7%, p = 0.05) and a drop in glycocholic acid (from 39.1 +/- 15.3% to 25.3 +/- 9.8%, p = 0.05) [26].

References