The Ursodeoxycholate Dose–Dependent Formation of Ursodeoxycholate–Glucuronide in the Rat and the Choleretic Potencies

Takikawa, Hajime; Sano, Naoyo; Narita, Tohru; Yamanaka, Masami

doi:10.1002/hep.1840110506

Cited by 20 publications

(8 citation statements)

References 29 publications

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“…By contrast, Hayakawa [28] reported that UDC markedly inhibited biliary cefotiam excretion in rats. The reason for this discrepancy may be due to his usage of a high dose of UDC, which we previously reported to cause exten sive glucuronidation of this bile acid [29,30]. Since 3-glyA-LC inhibited biliary CPM excre tion in the present study, UDC glucuronide may have inhibited biliary CPM excretion in his study [28].…”

Section: Discussionmentioning

confidence: 70%

Biliary Cef piramide Excretion: Its Relation to Biliary Excretion of Bile Acids and Sulfobromophthalein

Takikawa¹,

Uchida²,

Sano³

et al. 1995

Pharmacology

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Cefpiramide, a β-lactam antibiotic, has been reported to be excreted from hepatocytes into the bile by a carrier-mediated system. Herein, the relationship of biliary cefpiramide excretion to the excretion of bile acids and sulfobromophthalein was studied in rats. Biliary cefpiramide excretion was markedly inhibited by sulfobromophthalein, lithocholate-3-O-glucuronide and taurolithocholate-3-sulfate, whereas it was not inhibited by ursodeoxycholate or taurocholate. However, the inhibitory effect of cefpiramide on the biliary excretion of sulfobromophthalein or lithocholate-3-sulfate was very small. These findings indicate that, although cefpiramide is excreted by a process common to organic anions and bile acid sulfate and glucuronide, two or more excretory pathways for organic anions exist and cefpiramide has affinity for only one of these carriers.

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Section: Discussionmentioning

confidence: 70%

Biliary Cef piramide Excretion: Its Relation to Biliary Excretion of Bile Acids and Sulfobromophthalein

Takikawa¹,

Uchida²,

Sano³

et al. 1995

Pharmacology

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“…Any choleretic agent should increase bicarbonate output in bile by this mechanism. In our opinion, the experiments of Takikawa, Sano and Yamanaka (32) indicate that formation of the 3-glucuronide may occur during UDCAinduced hypercholeresis, but that the 3-glucuronide has exactly the expected choleretic activity of a bile acid 3-glucuronide and its formation is unlikely to play any causal role in the observed hypercholeresis. Thus, the experimental data of Takikawa, Sano and Yamanaka are completely in agreement with the views presented in this paper and with our previous papers dealing with hypercholeresis (2, 3, 5, 7 , 8 ) .…”

Section: Discussionmentioning

confidence: 70%

“…The choleretic activity of the taurine conjugate of nor-UDCA (5) and of UDCA (12) is similar to that of other taurine conjugates of the common natural bile acids. As noted above, Takikawa, Sano and Yamanaka have also reported that the 3-glucuronide of UDCA has choleretic properties similar to those of other bile acid amidates when allowance is made for the two negative charges of the 3-glucuronide (32). Hypercholeresis has also been attributed to stimulation of canalicular bicarbonate secretion by the accumulation of unconjugated UDCA in the hepatocyte (4, 10,11).…”

Section: Discussionmentioning

confidence: 85%

“…While this manuscript was undergoing review, Takikawa, Sano and Yamanaka (32) reported that during hypercholeresis induced in the Wistar rat by UDCA infusion, a considerable proportion (30%) of the UDCA was converted to the 34ethereal) glucuronide. They proposed that this polar metabolite was responsible for the observed hypercholeresis, because when the 3-ether glucuronide was prepared synthetically and infused into this strain of rats, it was considered to induce hypercholeresis.…”

Section: Discussionmentioning

confidence: 99%

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Hypercholeresis induced by unconjugated bile acid infusion correlates with recovery in bile of unconjugated bile acids

et al. 1991

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Using the isolated perfused rat and hamster liver, the relationship between bile flow, bile acid secretion rate and bile acid biotransformation after the injection of a small, bolus dose of radioactive ursodeoxycholate or of its C23 homolog, norursodeoxycholate, was examined. Ursodeoxycholate was promptly secreted into bile mostly as amino acid conjugates; less than 3% was secreted in unchanged form in the rat and less than 2% in the hamster. In contrast, norursodeoxycholate was secreted slowly, and biotransformed into glucuronide conjugates and unconjugated trihydroxy derivatives; it was also secreted in part in unchanged form. In the rat, 7% was secreted in unconjugated trihydroxy derivatives and 3% in unchanged form; in the hamster, 7% was secreted as unconjugated trihydroxy derivatives and 4% in unchanged form. The secreted bile acid species that showed the highest correlation with bile flow by far was always the unconjugated form in both rat and hamster. By multiple regression analysis, the apparent choleretic activity (microliters of induced bile flow per micromoles recovered bile acid molecules) indicated marked hypercholeresis for the unconjugated bile acid marked hypercholeresis for the unconjugated bile acid with values ranging from 100 to 300 microliters/mumol. Bile flow also correlated with total bile acid recovery for ursodeoxycholate in rat and norursodeoxycholate in hamster, but in all studies the apparent choleretic activity was far lower. Other calculations indicated that most bile flow during the first 30 min was induced by secretion of the unconjugated bile acid species in all experiments, the proportion ranging from 50% to 90%. The results indicate that when a bolus of ursodeoxycholate or norursodeoxycholate is presented to the perfused rodent liver, the secretion of the unchanged bile acid appears to be responsible for most of the bile flow, probably by a cholehepatic shunting mechanism.

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“…6B). Formation of CDC-gl was also confirmed by negative-ion fast-atom bombardment-mass spectrometry analysis of the bile according to the presence of m/z 567 and m/z 589, [M-HI-of dihydroxy bile acid glucuronide and its sodium salt, respectively, as previously reported (26,27). Table 2 summarizes the conjugation of [ 14C]CDC in the bile.…”

Section: Resultsmentioning

confidence: 91%

Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant sprague-dawley rat

et al. 1991

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The hepatic transport of bile acid conjugates was studied in the Eisai hyperbilirubinuria rat, a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Serum bile acid levels were increased, bile acid-independent bile flow was decreased and biliary glutathione concentrations were markedly decreased in the Eisai hyperbilirubinuria rat. Biliary excretion of sulfobromophthalein was markedly impaired and almost no glutathione conjugate was excreted in the bile of the Eisai hyperbilirubinuria rat. Biliary excretion of lithocholate-3-O-glucuronide and lithocholate-3-sulfate in the Eisai hyperbilirubinuria rat was markedly delayed, whereas that of lithocholate was only slightly delayed. After [14C]chenodeoxycholate infusion (1 mumol/min/100 gm for 60 min), the increases in bile flow and biliary excretion of isotope in the Eisai hyperbilirubinuria rat were not so prominent as those observed in control rats, and the glucuronide of chenodeoxycholate, which constituted about 15% of biliary chenodeoxycholate in control rats, was not observed in the Eisai hyperbilirubinuria rat. Initial uptake of lithocholate and its glucuronide and sulfate by isolated hepatocytes was not impaired in the Eisai hyperbilirubinuria rat; the profiles of cytosolic bile acid binding proteins in Eisai hyperbilirubinuria rat liver were identical to those in control liver. These data indicate that the Eisai hyperbilirubinuria rat has excretory impairment of organic anions, bile acid glucuronide and sulfate and that it has characteristics very similar to those of the hyperbilirubinemic mutant Wistar rats TR- and GY.

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The Ursodeoxycholate Dose–Dependent Formation of Ursodeoxycholate–Glucuronide in the Rat and the Choleretic Potencies

Cited by 20 publications

References 29 publications

Biliary Cef piramide Excretion: Its Relation to Biliary Excretion of Bile Acids and Sulfobromophthalein

Biliary Cef piramide Excretion: Its Relation to Biliary Excretion of Bile Acids and Sulfobromophthalein

Hypercholeresis induced by unconjugated bile acid infusion correlates with recovery in bile of unconjugated bile acids

Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant sprague-dawley rat

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