Ursodeoxycholic acid humans

The majority of micronuclei formed in this study were kinetochore negative, indicating a predominantly clastogenic effect of deoxycholic acid in these cells. Clastogenicity has previously been reported for organic fractions from human faeces and for ursodeoxycholic acid, utilising Chinese hamster ovary cells and human lymphocytes. 

E. Im and J. D. Martinez, Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/ERK signalling in human colon cancer cells, J. Nutr., 2004, 134, 483. 

In the bile cholesterol is kept soluble by fats, phospholipids like lecithin and by bile acids. The important bile acids in human bile are cholic acid, chen-odeoxycholic acid or chenodiol and ursodeoxycholic acid or ursodiol. Bile acids increase bile production. Dehydrocholic acid, a semisynthetic cholate is especially active in this respect. It stimulates the production of bile of low specific gravity and is therefore called a hydrocholeretic drug. Chenodiol and ursodiol but not cholic acid decrease the cholesterol content of bile by reducing cholesterol production and cholesterol secretion. Ursodiol also decreases cholesterol reabsorption. By these actions chenodiol and ursodiol are able to decrease the formation of cholesterolic gallstones and they can promote their dissolution. 

Lacaille, F., Paradis, K. The immunosuppressive effect of ursodeoxycholic acid a comparative in vitro study on human peripheral blood mononuclear cells. Hepatology 1993 18 165-172... 

AvUa MA, Berasain C, Torres L, Martfn-Duce A, Corrales FJ, Yang H, Prieto J (2000) Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol 33 907-914 Serviddio G, Pereda J, Pailardo FV, Carretero J, Borras C, Cutrin J, Vendemiale G, Poli G, Vina J, Sastre J (2004) Ursodeoxycholic acid protects against secondary biliary cirrhosis via up-regulation of y-glutamyl cysteine synthetase and prevention of mitochondrial oxidative stress. Hepatology (in press)... 

Ursodeoxycholic acid (3a,7p-dihydroxy-5p-cholan-24-oic acid) is present in human bile in small quantities and is of interest because of its therapeutic use as a gallstone-dissolving agent (D8). This bile acid is thought to be... 

F7. Fromm, H., Sarva, R. P., and Bazzoli, F., Formation of ursodeoxycholic acid from chenodeoxycholic acid in the human colon studies of the role of 7-ketolithocholic acid as an intermediate. /. Lipid Res. 24, 841-853 (1983). 

Tessier, E. Neirinck, L. Zhu, Z. High-performance liquid chromatographic mass spectrometric method for the determination of ursodeoxycholic acid and its glycine and taurine conjugates in human plasma. J. Chromatogr. B, 2003, 798... 

Both compounds have been fed to fasting human volunteers at a dose corresponding to 300 mg of free drug, and the plasma levels of ursodeoxycholic acid determined over a 12 hrs period, and compared with those obtained with an equivalent dose of the free drug. 

Ursodeoxycholic acid was detected very early by Hammarsten in polar bear bile (85). It was isolated in crystalline form by Shoda (58) and characterized later by Iwasaki (84). The acid, which is the 7/3-epimer of chenodeoxycholic acid, may be prepared in good yield from 7-ketolithocholic acid by reduction with sodium in propanol according to Kanazawa et al. (86). Ursodeoxycholic acid was originally considered to be a unique constituent of bear bile but has since been detected as a minor constituent in the bile of several mammals including man (2). It is also present in human feces (52). 

Quantitative Determination of Ursodeoxycholic Acid and Its Deuter-ated Derivative in Human Bile by Gas Chromatography-Mass Fragmento-graphy... 

Figure 8 A pharmacophore for the human hepatic sodium-dependent bile acid transporter using eight molecules and IC50 values demonstrating two hydrophobic features (bottom right) and two hydrogen-bond donors (top left and top right). The observed versus predicted data resulted in a correlation r = 0.97. A training set member (ursodeoxycholic acid) is shown fitted to this pharmacophore.

Nakayama/ K. Myazaki A. Koga, Effect of chenodeoxycholic and ursodeoxycholic acids on isolated human hepatocytes. Gastroenterology 78 1228 (1980) abstr. 

The most prominent BA present in human are cholic acid (C), chenodeoxy-cholic acid (CDC), deoxycholic acid (DC), lithocholic acid (LC), and ursodeoxycholic acid (UDC), as derivatives of 5p-cholan-24-oic acid. Primarily they are present as glycine and taurine conjugates, with the conjugation occurring at carbon 24 of the structure. In addition to the above major BA, a wide array of minor components has been identified. 

Bile acids contain hydroxyl groups, which are usually substituted at positions, C-3, C-7, or C-12 of the steroid nucleus. The three major bile acids found in man are 3a,7a,12a-trihydroxy-5P-cholan-24-oic acid 3a,7a-dihydroxy-5p-cholan-24-oic add and 3a,12a-dihydroxy-5p-cholan-24-oic acid. Because of the complexities of steroid nomenclature, bile acids are nearly always referred to by trivial names. 11108, the three major human bile acids are named cholic acid, chenodeoxycholic acid, and deoxycholic acid, respectively, and their chemical structures are shown in Fig. 1. Human bile does, however, contain small amounts of other bile acids, such as lithocholic acid (3a-hydroxy-5P-cholan-24-oic add) and ursodeoxycholic add (3a,7p-dihydroxy-5p-cholan-24-oic acid) (see Fig. 1). 

In normal human liver (7 samples) identified bile acids were cholate (54%), chenodeoxycholate (28%), and deoxycholate (18%) [12]. With a more sensitive system of analysis (glass capillary gas chromatography-mass spectrometry and selected ion monitoring) the values reported for 5 bile acids from 10 samples of normal human bile [14] were cholate (41%), chenodeoxycholate (39%), deoxycholate (15%), ursodeoxycholate (4%), and lithocholate (1%). 

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