Bile acid excretion: the alternate pathway in the hamster (original) (raw)
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Hepatology, 1985
In patients with hepatobiliary diseases, considerable amounts of sulfated and glucuronidated bile acids are excreted in urine. Information on the biliary excretion of these compounds is lacking. We used an intestinal perfusion method to determine the biliary excretion of sulfated and glucuronidated bile acids in eight patients with alcoholic cirrhosis and moderately severe cholestasis and compared results with urinary excretion rates. In bile, the patients excreted 508.7 pmoles per hr (mean) nonsulfated, nonglucuronidated bile acids, 8.1 pmoles per hr sulfated bile acids and 4.0 pmoles per hr glucuronidated bile acids. In urine, these patients excreted 0.27 pmoles per h r nonsulfated, nonglucuronidated bile acids, 0.88 pmoles per hr sulfated bile acids and 0.02 pmoles per hr glucuronidated bile acids. Sulfates and glucuronides of mono-, di-and trihydroxy bile acids were detected in urine and bile. In urine, tetrahydroxy bile acids were only excreted as nonsulfated and nonglucuronidated forms. The bi1e:urine excretion ratio of sulfated bile acids was 9:l and of glucuronidated bile acids was 226: 1. In alcoholic cirrhosis with cholestasis, biliary excretion is an important excretory route of sulfated and glucuronidated bile acids. The following list of acids was used throughout: lithocholic acid, 3ahydroxy-5@-cholan-24-oic acid; chenodeoxycholic acid, 3a,7a-dihydroxy-5fl-cholan-24-oic acid; ursodeoxycholic acid, 3a,7@-dihydroxy-5@-cholan-24-oic acid; hyodeoxycholic acid, 3a,6a-dihydroxy-5@-cholan-24-oic acid; deoxycholic acid, 3a,7a-dihydroxy-5@-cholan-24-oic acid; cholic acid, 3a,7a,l2a-trihydroxy-5~-cholan-24-oic acid; hyocholic acid, 3a,6a,7a-trihydroxy-5@-cholan-24-oic acid.
Urinary excretion of bile acids during acute administration in man
European Journal of Clinical Investigation, 1988
Six healthy subjects, 45-72 years old, received a 10-day feeding of 750 mg of two of the following bile acids: deoxycholate (DCA), chenodeoxycholate (CDCA), cholate (CA), hyodeoxycholate (HDCA), ursodeoxycholate (UDCA), and ursocholate (UCA). The urinary excretion of total bile acids was low during administration of lipophilic bile acids (DCA and CDCA), when serum levels show low postabsorption peaks. Instead, hydrophilic bile acids (UDCA and above all HDCA) were heavily excreted in the urine as sulphates and glucuronides, and serum levels reach high values. Only UCA, strongly hydrophilic, was predominantly excreted as unconjugated fractions. Thus, the physicochemical properties of bile acids (as measured by both the partition between octanol and water, and the water solubility) were factors that influenced the route of bile acid elimination from the body, whereas their conjugation was not always requested for urinary excretion.
Altered bile acid metabolism in primary biliary cirrhosis
Digestive Diseases and Sciences, 1981
Selected aspects of bile acid metabolism were assessed in six women with primary biliary cirrhosis and varying degrees of cholestasis. Urinary bile acid excretion was markedly increased and correlated highly with serum levels. In three patients in whom urinary bile acids were separated by chromatography, the majority of urinary bile acids were monosulfated (34%, 42%, 32%) or polysulfated and~or glucuronidated (30%, 20%, 38%). The monosulfates of chenodeoxycholic acid were conjugated at either the 3 position (67%, 68%, 73%) or the 7 position (33%, 32%, 27%); similarly, the monosulfates of cholic cicid were conjugated at the 3 position (65%, 58%, 68%) or the 7position (35%, 42%, 32%). The position of sulfation was not markedly influenced by the mode of amidation with glycine or taurine. Chenodeoxycholic exchangeable pool size, turnover rate, and synthesis were measured by isotope dilution and found to be well within normal limits, despite the cholestasis. The fraction of chenodeoxycholic acid synthesis excreted in urine ranged from 9 to 48%; 4-38% of chenodeoxycholic acid synthesis was sulfated. These data indicate that the major abnormalities in bile acid metabolism in patients with cholestasis secondary to primary biliary cirrhosis are formdtion of sulfated bile acids in greatly increased amounts, elevation of blood levels of primary bile acids, and a shift to renal excretion aS a major mechanism for bile acid elimination. Chenodeoxycholic acid Synthesis continues at its usual rate despite cholestasis. Whether these changes, including the formation of 7-monosulfated bile acids, occur in other forms of cholestasis and whether either" the persistance of unchanged chenodeoxycholic acid synthesis or the formation of such novel conjugates has any pathophysiological significance remain to be investigated.
World Journal of Gastroenterology, 2008
During the last decades the concept of bile secretion as merely a way to add detergent components to the intestinal mixture to facilitate fat digestion/absorption and to eliminate side products of heme metabolism has evolved considerably. In the series of mini-reviews that the World Journal of Gastroenterology is to publish in its section of "Highlight Topics", we will intend to give a brief but updated overview of our knowledge in this field. This introductory letter is intended to thank all scientists who have contributed to the development of this area of knowledge in gastroenterology.
Hepatic uptake and biliary secretion of bile acids in the perfused rat liver
Pharmacological Research, 1992
Hepatic uptake and biliary secretion have been evaluated in the isolated perfused rat liver for cholic, chenodeoxycholic, ursodeoxycholic acid, both free and taurine-conjugated; the physicochemical properties of the bile acids have also been calculated and related to these experimental parameters. Cholic acid disappearance rate from the perfusate was the fastest, followed by that of ursodeoxycholic and chenodeoxycholic; it was also faster for taurine-conjugated bile acids than for their respective unconjugated forms. The recovery in bile was higher for conjugated than for unconjugated bile acids, and, among each class, was higher for cholic than for chenodeoxycholic and ursodeoxycholic. The hepatic uptake correlated negatively (r=-0.99) with the bile acid lipophilicity, while the biliary secretion correlated with the solubility of the molecules. These results show the effect of the physicochemical properties of BA on their hepatic handling, at the physiological concentration of BA in the portal blood.
Bile salt-associated electrolyte secretion
Experimental and Toxicologic Pathology, 1992
The mechanisms involved in bile salt-induced choleresis are poorly known. To give an insight in this physiological process, bile salt-associated electrolyte secretion was studied following relief of a short-term (2 h) biliary .obstruction in the rat, an experimental model that shows an important diminution of bile salt choleretic efficiency. For this purpose, biliary excretion of total bile salts and electrolytes (sodium, chloride and bicarbonate) were studied in such a model during taurocholate infusion at increasing rates. The results showed that bile flow, bile salt output and electrolyte secretion stimulated by taurocholate,administration were decreased in the rats that were subjected to biliary obstruction. Besides, the choleretic efficiency of the excreted bile salts, as estimated by the slope of the regression line of bile flow vs. bile salt output, was diminished by 46 % (p < 0.005). Multiple regression analysis of bile flow vs. bile salt and electrolyte outputs allowed to detect a selective diminution of the fraction of bile flow related to bile salt-associated electrolyte secretion ("secretory fraction" of the choleretic efficiency of bile salts) (3.2 ± 0.3 vs. 2.5 ± 0.2L1mol, p < 0.05) whereas the "osmotic fraction" of the choleretic efficiency of bile salts was not modified by the treatment (5. a ± 0.4 vs. 5.1 ± 0.3 Llmol, p> 0.05). Since both chloride and bicarbonate biliary concentrations in the volume of bile stimulated by taurocholate were reduced by 53 % and 52 % respectively, a role of these anions in the generation of bile salt-induced choleresis was suggested. Possible mechanisms involved in such a process and in its early impairment during cholestasis are discussed.
Bile acid-induced liver toxicity: Relation to the hydrophobic-hydrophilic balance of bile acids
Medical Hypotheses, 1986
Hypertransaminasemia is a frequent side effect during chenodeoxycholic administration for gallstone dissolution. Evidence suggests that this effect is not mediated by lithocholic acid, the intestinal metabolite of chenodeoxycholic acid, but that toxicity is due to the chenodeoxychol~c acid itself. In vitro cytotoxicity of bile salts is positively proportional to their detergent effect, which is, on the other hand, related to their hydrophobic-hydrophilic balance. We hypothesize that in vivo also liver injury can occur when the liver is perfused by an high proportion of strongly detergent bile salts. The more detergent bile salts are unconjugated or glycine conjugated, while the lesser are taurine conjugated and sulfated. Within each class the following order of decreasing detergent power can be indicated: lithocholic) deoxycholic) chenodeoxycholic > cholic > ursodeoxycholic acid. Besides chronic exogenous administration of chenodeoxycholic or deoxycholic acids, conditions in which the liver is perfused by an high mass of highly detergent bile salts are those characterized by an enhanced intestinal biodegradation of bile salts. These conditions, which are common features of some chronic inflammatory bowel diseases, are frequently associated with liver damage. On the other hand, a normally detergent bile salt pool can become hepatotoxic for liver cells which have already been injured. In this respect, as already reported for increased sulfation, the increased proportion of taurine conjugates and the reduced formation of deoxycholic acid in liver cirrhosis can be regarded as protective mechanisms. Liver toxicity induced by bile salts' detergency can be prevented by favouring tauroconjugation or reducing the intestinal degradation of bile salts or by administering poorly detergent bile salts.