Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids

Stiehl, A.; Raedsch, R.; Rudolph, G

doi:10.1016/0016-5085(90)90834-n

Cited by 112 publications

(46 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Taken together with previous observations, (a) TUDCA, but not taurocholic acid induces a sustained [Ca++]i increase at low physiologic levels (10), (b) TUDCA, but not taurocholic acid stimulates sustained, Ca++-dependent vesicular exocytosis at physiologic levels, and (c) long-term administration of UDCA in patients with cholestatic liver diseases leads to gradual improvement of cholestatic features (1)(2)(3) and to replacement ofthe least potent Ca++ mobilizing bile acid conjugates of cholic acid by the most potent Ca++ mobilizing conjugates of UDCA (8,58,59). We speculate that the Ca++ mobilizing effect of UDCA conjugates may gradually (re-)activate the impaired process of hepatocellular vesicular exocytosis in cholestatic liver.…”

Section: Resultsmentioning

confidence: 99%

Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis.

Beuers¹,

Nathanson²,

Isales³

et al. 1993

J. Clin. Invest.

162

131

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis.

Beuers¹,

Nathanson²,

Isales³

et al. 1993

J. Clin. Invest.

162

131

View full text Add to dashboard Cite

show abstract

“…[7][8][9][10][11][12][23][24][25] The mechanism of action of UDCA in hepatobiliary diseases is still not completely understood. 26 -38 Decreased intestinal absorption of hydrophobic, hepatotoxic bile acids, 39,40 and biliary enrichment with hydrophilic, nontoxic UDCA changes the balance of biliary bile acids in favor of nontoxic hydrophilic bile acids, and this change may represent one of the mechanisms of action of UDCA. 13 In patients, studies on biliary enrichment are difficult to perform.…”

Section: Discussionmentioning

confidence: 99%

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

et al. 2004

View full text Add to dashboard Cite

Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseases. In primary sclerosing cholangitis (PSC), there is evidence that high doses (؎20 mg/kg) of UDCA may be more effective than average doses. Biliary enrichment of UDCA at such high doses may represent the decisive factor for its beneficial effect. Up to now it is not clear how high-dose UDCA correlates with its biliary enrichment and whether bacterial degradation of large amounts of UDCA may lead to an increased bacterial formation of more toxic hydrophobic bile acids. We determined the biliary bile acid composition in 56 patients with PSC including 30 patients with repeat bile samples treated with various doses of UDCA. At a UDCA dose of 10 -13 mg/kg/d (n ‫؍‬ 18) biliary UDCA represented 43.1% ؉ 0.3% (mean ؉ SD) of total bile acids; at a UDCA dose of 14 -17 mg/kg (n ‫؍‬ 14), its biliary content increased to 46.9% ؉ 0.3%, at 18 -21 mg/kg (n ‫؍‬ 34) to 55.9% ؉ 0.2%, at 22-25 mg/kg (n ‫؍‬ 12) to 58.6% ؉ 2.3%, and at 26 -32 mg/kg (n ‫؍‬ 8) to 57.7% ؉ 0.4%. During UDCA treatment, the biliary content of all other bile acids was unchanged or decreased. In conclusion, biliary enrichment of UDCA increases with increasing dose and reaches a plateau at 22-25 mg/kg. There was no increase of toxic hydrophobic bile acids. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, it seems likely that UDCA doses of up to 22-25 mg/kg may be more effective than lower doses. (HEPATOLOGY 2004;40:693-698.)

show abstract

“…attributed to decreased uptake of common bile salts from the small intestine 18 leading to increased bacterial 7␣-dehydroxylation of the primary bile salt CA. Increase in Oatp2 expression in response to bile salt feeding was not due to recruitment of periportal hepatocytes as judged by immunofluorescence.…”

Section: Discussionmentioning

confidence: 99%

“…Biliary bile salt composition was determined by gas-liquid chromatography as described previously. 18 Antibodies. The rabbit polyclonal antibodies K4, K10, K12, K15, and K22 were raised against the carboxyl terminus of rat Ntcp, Oatp1, Bsep, Oatp2, and Oatp4, respectively.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Rat Organic Anion Transporters in Bile Salt–Induced Cholestatic Hepatitis: Effect of Ursodeoxycholate

et al. 2003

View full text Add to dashboard Cite

Hepatic uptake of organic anions, including bile salts, is mediated by members of the organic anion-transporting polypeptide (Oatp) family. In rat liver, Oatp1 (Slc21a1), Oatp2 (Slc21a5), and Oatp4 (Slca10) are expressed at the basolateral membrane of hepatocytes and may be differentially regulated under pathophysiologic conditions such as cholestasis. The aim of this study was to determine the effects of cholic acid (CA) and ursodeoxycholic acid (UDCA) on the expression of Oatp4 compared with Ntcp, Oatp1, and Oatp2. Wistar rats were fed with CA (0.5%) or both CA (0.5%) and UDCA (0.25%) for 3 weeks. Oatp expression was studied by Northern and Western blot analysis as well as immunofluorescence analysis. Transport function was compared measuring biliary secretion of 14 C-CA and 14 Ctaurocholic acid (TCA). In CA-fed animals, biliary secretion of 14 C-CA and 14 C-TCA was markedly delayed over 40 minutes compared with controls. Accordingly, Oatp4 protein was significantly down-regulated in CA-fed animals together with Oatp1 and Ntcp. Cofeeding of CA plus UDCA prevented the impairment of 14 C-CA and 14 C-TCA secretion and the downregulation of Oatp4. Oatp4 messenger RNA (mRNA) levels did not differ significantly between bile salt-fed groups, suggesting a posttranscriptional effect of CA on Oatp4 expression. In contrast to Oatp1 and Oatp4, Oatp2 protein expression was increased by CA feeding, indicating a differential regulation of Oatp transporters. In conclusion, we show that CA feeding may cause cholestasis associated with a posttranscriptional down-regulation of Oatp4. UDCA may prevent impairment of hepatic function by restoring hepatic transporter expression. (HEPATOLOGY 2003;38:187-195.)

show abstract

Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids

Cited by 112 publications

References 24 publications

Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis.

Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis.

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

Regulation of Rat Organic Anion Transporters in Bile Salt–Induced Cholestatic Hepatitis: Effect of Ursodeoxycholate

Contact Info

Product

Resources

About