Chenodeoxycholic acid CDCA

Figure 5.2 Therapeutic interventions for decreasing colorectal mucosal bile acid exposure as a CRC chemoprevention strategy. 1) Lifestyle modifications including reduction in dietary animal fat and increased fibre intake may, at least partly, be explained by reduction in luminal primary (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary (deoxycholic acid [DCA] and lithocholic acid [LCA]) bile acids. 2) Reduction of secondary bile acids, which are believed to have pro-carcinogenic activity could be obtained by decreased bacterial conversion from primary bile acids. 3) Alternatively, bile acids could be sequestered by chemical binding agents, e.g. aluminium hydroxide (Al(OH)3) or probiotic bacteria. 4) Exogenous ursodeoxycholic acid (UDCA) can reduce the luminal proportion of secondary bile acids and also has direct anti-neoplastic activity on colonocytes in vitro.

Bile acids are also natural ligands for the farnesoid X receptor (FXR), a receptor that belongs to the nuclear hormone receptor superfamily. The hydrophobic bile acid chenodeoxycholic acid (CDCA) is the most potent... 

Igimi et al ) have predicted that the precipitation of GUDC could occur during treatment with GUDC. Bateson et al°I have reported that 122 patients with cholesterol gall stones vrfiich can not take the picture even by Roentgen were treated with chenodeoxycholic acid(CDCA) cind 56 patients were treated with ursodeoxycholic acid(UDCA) for six months or more. Six of the 56 patients treated with UDCA developed calcification, but none of the patients treated with CDCA showed any evidence of calcification on the surface of the... 

Primary BAs, cholic acid (CA), and chenodeoxycholic acid (CDCA), are synthesised via the 5/3-saturation of the cholesterol double bond by enzymes of the hepa-tocyte microsomal fraction, epimerisation of the 3/j-hydroxyl group to the 3a-con-figuration, and further insertion of a 7 -hydroxyl group, with or without a further 12a-hydroxyl group. After shortening of the side chain by three carbons, oxidation of the terminal carbon of the side chain occurs to form the carboxylic group [3]. Alternative metabolic sequences add to the complexity of this metabolic pathway (Fig. 5.4.2). 

It is well known that bile acids are produced in the liver of vertebrates for digestion and absorption of fats and fat-soluble vitamins. Starting from isoprene, a series of biochemical reactions yield a key compound, cholesterol, which is converted to primary bile acids, such as cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA) and lithocholic acid (LCA). Hereafter the abbreviations of bile acid derivatives can be seen by consulting Table 1 and Figure 1. 

Scalia and Games developed a packed column SFC method for the analysis of free bile acids cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) [32]. The baseline separation of all five bile acids was achieved on a packed phenyl column with a methanol-modified carbon dioxide in less than 4 min. The elution order showed a normal-phase mechanism because the solutes eluted in the order of increasing polarity following the number of hydroxyl groups on the steroid nucleus. The method was also applied to the assay of UDCA and CDCA in capsule and tablet formulations. The method was found to be linear in the range 1.5-7.5 ng/ml (r > 0.99, n = 6). The average recoveries (n= 10) for UDCA and CDCA were 100.2% with a RSD of 1.7% and 101.5% with a RSD of 2.2%, respectively. The reproducibility of the method was less than 1.5% (n = 10) for both UDCA and CDCA. 

Dried bile from the Himalayan bear (Yutan) has been used for centuries in China to treat liver disease. UDCA (ursodiol, Actigall) is a hydrophilic, dehydroxylated bile acid that is formed by epimerization of the bile acid, chenodeoxycholic acid (CDCA Chenodiol), in the gut by intestinal bacteria. It comprises approximately 1 to 3% of the total bile acid pool in human beings but is present at much higher concentrations in bears. When administered orally, litholytic bile acids, such as chenodiol and ursodiol, can alter relative concentrations of bile acids, decrease biliary lipid secretion, and reduce the cholesterol content of the bile so that it is less lithogenic. Ursodiol also may have cytoprotective effects on hepatocytes and effects on the immune system that account for some of its beneficial effects in cholestatic liver diseases. 

Chenodeoxycholic acid CDCA (3 ,7a-dihydroxy-cholanoic acid) 392.56 143 1.20... 

The effect of chenodeoxycholic acid (CDCA) on cholesterol absorption. Gastroenterology, 77 223 (1979). 

---