23-methyl-3α,7β-dihyroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat

A. R. Roda, R. Aldini, B. Grigolo, P. Simoni, E. Roda, R. Pellicciari, P. L. Lenzi, B. Natalini

Research output: Contribution to journalArticle

Abstract

A side chain derivative of ursodeoxycholic acid, 23-methylursodeoxycholic acid, was synthesized and the effect of i.v. infusion of the acid at different doses (0.75, 1.5, 3.0 and 6.0 μmoles per min per kg body weight over 1 hr) on bile flow, on its hepatic biotransformations and on biliary lipid secretion has been studied in bile fistula rats. The results were compared with those of ursodeoxycholic and cholid acid administered under similar conditions. 23-Methylursodeoxycholic acid is poorly secreted into bile and poorly taurine and glycine conjugated, at all infusion doses. Ursodeoxycholic acid is quantitatively recovered at low doses and recovered less at high infusion rates. Cholic acid is almost entirely recovered at all infusion doses. Ursodeoxycholic acid conjugation pattern is dependent on the dose, and glucuronidation and sulfation operate at high doses. Cholic acid is taurine conjugated at low doses; at high doses, large amounts of unconjugated bile acids are observed. Methylursodeoxycholic acid presents a delayed secretion and hypercholeresis. Ursodeoxycholic acid presents similar results at high infusion rates, possibly by reaching a high intrahepatic concentration of free form. The octanol/water partition coefficients of ursodeoxycholic acid and 23-methylursodeoxycholic acid are similar and higher than that of cholic acid. A chole-hepatic shunting of 23-methylursodeoxycholic acid may explain both the low recovery in bile and hypercholeresis and is consistent with its hydrophobicity. The high water solubility and hydrophilicity of cholic acid, on the contrary, makes possible its high recovery in bile. The effect on biliary lipid secretion is unpredictable and affected by the dose and, in consequence, by the conjugation pattern of the bile acid. The detergency of the intrahepatic pool of the secreted bile acid and the physicochemical state of the native bile may be driving force determinant for cholesterol and phospholipid biliary secretion.

Original languageEnglish
Pages (from-to)1571-1576
Number of pages6
JournalHepatology
Volume8
Issue number6
Publication statusPublished - 1988

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Ursodeoxycholic Acid
Bile
Cholic Acid
Acids
Bile Acids and Salts
Taurine
Hydrophobic and Hydrophilic Interactions
Lipids
Octanols
Water
Liver
Biotransformation
Solubility
Glycine
Fistula
Phospholipids
Cholesterol
Body Weight
23-methylursodeoxycholic acid

ASJC Scopus subject areas

  • Hepatology

Cite this

Roda, A. R., Aldini, R., Grigolo, B., Simoni, P., Roda, E., Pellicciari, R., ... Natalini, B. (1988). 23-methyl-3α,7β-dihyroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat. Hepatology, 8(6), 1571-1576.

23-methyl-3α,7β-dihyroxy-5β-cholan-24-oic acid : Dose-response study of biliary secretion in rat. / Roda, A. R.; Aldini, R.; Grigolo, B.; Simoni, P.; Roda, E.; Pellicciari, R.; Lenzi, P. L.; Natalini, B.

In: Hepatology, Vol. 8, No. 6, 1988, p. 1571-1576.

Research output: Contribution to journalArticle

Roda, AR, Aldini, R, Grigolo, B, Simoni, P, Roda, E, Pellicciari, R, Lenzi, PL & Natalini, B 1988, '23-methyl-3α,7β-dihyroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat', Hepatology, vol. 8, no. 6, pp. 1571-1576.
Roda AR, Aldini R, Grigolo B, Simoni P, Roda E, Pellicciari R et al. 23-methyl-3α,7β-dihyroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat. Hepatology. 1988;8(6):1571-1576.
Roda, A. R. ; Aldini, R. ; Grigolo, B. ; Simoni, P. ; Roda, E. ; Pellicciari, R. ; Lenzi, P. L. ; Natalini, B. / 23-methyl-3α,7β-dihyroxy-5β-cholan-24-oic acid : Dose-response study of biliary secretion in rat. In: Hepatology. 1988 ; Vol. 8, No. 6. pp. 1571-1576.
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abstract = "A side chain derivative of ursodeoxycholic acid, 23-methylursodeoxycholic acid, was synthesized and the effect of i.v. infusion of the acid at different doses (0.75, 1.5, 3.0 and 6.0 μmoles per min per kg body weight over 1 hr) on bile flow, on its hepatic biotransformations and on biliary lipid secretion has been studied in bile fistula rats. The results were compared with those of ursodeoxycholic and cholid acid administered under similar conditions. 23-Methylursodeoxycholic acid is poorly secreted into bile and poorly taurine and glycine conjugated, at all infusion doses. Ursodeoxycholic acid is quantitatively recovered at low doses and recovered less at high infusion rates. Cholic acid is almost entirely recovered at all infusion doses. Ursodeoxycholic acid conjugation pattern is dependent on the dose, and glucuronidation and sulfation operate at high doses. Cholic acid is taurine conjugated at low doses; at high doses, large amounts of unconjugated bile acids are observed. Methylursodeoxycholic acid presents a delayed secretion and hypercholeresis. Ursodeoxycholic acid presents similar results at high infusion rates, possibly by reaching a high intrahepatic concentration of free form. The octanol/water partition coefficients of ursodeoxycholic acid and 23-methylursodeoxycholic acid are similar and higher than that of cholic acid. A chole-hepatic shunting of 23-methylursodeoxycholic acid may explain both the low recovery in bile and hypercholeresis and is consistent with its hydrophobicity. The high water solubility and hydrophilicity of cholic acid, on the contrary, makes possible its high recovery in bile. The effect on biliary lipid secretion is unpredictable and affected by the dose and, in consequence, by the conjugation pattern of the bile acid. The detergency of the intrahepatic pool of the secreted bile acid and the physicochemical state of the native bile may be driving force determinant for cholesterol and phospholipid biliary secretion.",
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T1 - 23-methyl-3α,7β-dihyroxy-5β-cholan-24-oic acid

T2 - Dose-response study of biliary secretion in rat

AU - Roda, A. R.

AU - Aldini, R.

AU - Grigolo, B.

AU - Simoni, P.

AU - Roda, E.

AU - Pellicciari, R.

AU - Lenzi, P. L.

AU - Natalini, B.

PY - 1988

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N2 - A side chain derivative of ursodeoxycholic acid, 23-methylursodeoxycholic acid, was synthesized and the effect of i.v. infusion of the acid at different doses (0.75, 1.5, 3.0 and 6.0 μmoles per min per kg body weight over 1 hr) on bile flow, on its hepatic biotransformations and on biliary lipid secretion has been studied in bile fistula rats. The results were compared with those of ursodeoxycholic and cholid acid administered under similar conditions. 23-Methylursodeoxycholic acid is poorly secreted into bile and poorly taurine and glycine conjugated, at all infusion doses. Ursodeoxycholic acid is quantitatively recovered at low doses and recovered less at high infusion rates. Cholic acid is almost entirely recovered at all infusion doses. Ursodeoxycholic acid conjugation pattern is dependent on the dose, and glucuronidation and sulfation operate at high doses. Cholic acid is taurine conjugated at low doses; at high doses, large amounts of unconjugated bile acids are observed. Methylursodeoxycholic acid presents a delayed secretion and hypercholeresis. Ursodeoxycholic acid presents similar results at high infusion rates, possibly by reaching a high intrahepatic concentration of free form. The octanol/water partition coefficients of ursodeoxycholic acid and 23-methylursodeoxycholic acid are similar and higher than that of cholic acid. A chole-hepatic shunting of 23-methylursodeoxycholic acid may explain both the low recovery in bile and hypercholeresis and is consistent with its hydrophobicity. The high water solubility and hydrophilicity of cholic acid, on the contrary, makes possible its high recovery in bile. The effect on biliary lipid secretion is unpredictable and affected by the dose and, in consequence, by the conjugation pattern of the bile acid. The detergency of the intrahepatic pool of the secreted bile acid and the physicochemical state of the native bile may be driving force determinant for cholesterol and phospholipid biliary secretion.

AB - A side chain derivative of ursodeoxycholic acid, 23-methylursodeoxycholic acid, was synthesized and the effect of i.v. infusion of the acid at different doses (0.75, 1.5, 3.0 and 6.0 μmoles per min per kg body weight over 1 hr) on bile flow, on its hepatic biotransformations and on biliary lipid secretion has been studied in bile fistula rats. The results were compared with those of ursodeoxycholic and cholid acid administered under similar conditions. 23-Methylursodeoxycholic acid is poorly secreted into bile and poorly taurine and glycine conjugated, at all infusion doses. Ursodeoxycholic acid is quantitatively recovered at low doses and recovered less at high infusion rates. Cholic acid is almost entirely recovered at all infusion doses. Ursodeoxycholic acid conjugation pattern is dependent on the dose, and glucuronidation and sulfation operate at high doses. Cholic acid is taurine conjugated at low doses; at high doses, large amounts of unconjugated bile acids are observed. Methylursodeoxycholic acid presents a delayed secretion and hypercholeresis. Ursodeoxycholic acid presents similar results at high infusion rates, possibly by reaching a high intrahepatic concentration of free form. The octanol/water partition coefficients of ursodeoxycholic acid and 23-methylursodeoxycholic acid are similar and higher than that of cholic acid. A chole-hepatic shunting of 23-methylursodeoxycholic acid may explain both the low recovery in bile and hypercholeresis and is consistent with its hydrophobicity. The high water solubility and hydrophilicity of cholic acid, on the contrary, makes possible its high recovery in bile. The effect on biliary lipid secretion is unpredictable and affected by the dose and, in consequence, by the conjugation pattern of the bile acid. The detergency of the intrahepatic pool of the secreted bile acid and the physicochemical state of the native bile may be driving force determinant for cholesterol and phospholipid biliary secretion.

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