Erythritol and mannitol clearances with taurocholate and secretin-induced cholereses.

Barnhart, James L.; Combes, Burton

doi:10.1152/ajpendo.1978.234.2.e146

Cited by 24 publications

(19 citation statements)

References 12 publications

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“…Although recent studies in dog and rhesus monkey indicate that erythritol clearance may not accurately reflect the magnitude of, canalicular bile production (26,27), this procedure is the best method currently available. A direct relationship between bile flow and erythritol clearance was observed which qualitatively suggests that the choleresis induced by VPA is largely of canalicular origin.…”

Section: Discussionmentioning

confidence: 99%

Choleretic effect of valproic acid in the rat

Watkins

Klaassen

1981

Hepatology

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Valproic acid (VPA) is an anticonvulsant agent which produced marked choleresis in the rat. Bile flow rate increased from 50 to 60 microliter per min per kg to 120 to 145 microliter per min per kg immediately after i.v. injection of VPA (37.5 to 150 mg per kg; 2 ml per kg) in male Sprague-Dawley rats. The duration of maximal bile flow was dose-dependent and increased from 30 min (37.5 mg VPA per kg) to approximately 2 hr (150 mg VPA per kg). Choleresis diluted the biliary concentrations of bile acids, Cl-, cholesterol, and phospholipids. VPA did not change the bile/plasma ratio for erythritol suggesting that the increased bile flow is of canalicular origin. VPA did not influence the excretion of bile acids or their osmotic activity, whereas bile salt-independent flow doubled in rats treated with 150 mg VPA per kg. The bile/plasma, bile/liver, and liver/plasma concentration ratios for VPA were 11.7, 1.6, and 7.3, respectively. Approximately 90% of VPA appearing in bile was biotransformed, primarily as a glucuronide. Bile flow correlated with VPA excretion; 16 microliter of bile was produced per micromole VPA which suggests that choleresis is primarily due to the osmotic activity of VPA metabolites in bile. VPA enhanced the excretion of inorganic ions which may also contribute to choleresis. Biliary excretion of phenol-3,6-dibromophthalein disulfonate and ouabain was unaffected. Thus, VPA is an effective choleretic which stimulates bile salt-independent flow of canalicular origin largely as a consequence of the osmotic properties of VPA conjugates in bile.

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Section: Discussionmentioning

confidence: 99%

Choleretic effect of valproic acid in the rat

Watkins

Klaassen

1981

Hepatology

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“…The tight junctions between hepatocytes are cation selective, allowing free movement of Na + , and are impermeable to bile salts and glucuronides. However, these junctions allow passage of small nonelectrolytes such as erythritol, mannitol,122 and sucrose,123 suggesting that they are large enough to permit appreciable osmotic water flow during bile fluid formation.…”

Section: Cholestasis and Bile Duct Obstructionmentioning

confidence: 99%

Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

Levitt¹,

Levitt²

2014

CEG

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Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB) and unconjugated bilirubin (UB). While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis), and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert’s, Dubin–Johnson, Crigler–Najjar, Rotor syndromes). Novel aspects of this review include: 1) quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2) detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3) discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4) pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5) role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6) insights concerning the clinical interpretation of bilirubin measurements.

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“…The results reported herein, which include data from some of the previous experiments (13) and from 19 new puppies and four fed adult dogs, are fully consistent with those already published. However, since I4C-erythritol biliary clearance may not accurately measure canalicular bile flow (27,28), these conclusions must be made with considerable caution. Indeed, it is quite likely that, as in other species (29,30), '4C-erythritol permeates the biliary ductules/ducts in the dog as well, and the permeability of these distal structures to such a solute may be greater in the newborn puppy than in the adult animal.…”

Section: Spontaneozls Bilefi~rmationmentioning

confidence: 99%

Bile Secretion and its Control in the Newborn Puppy

Tavoloni

1986

Pediatr Res

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ABSTRACT. To gain information about the ontogeny of neonatal biliary physiology, we determined gallbladder bile composition, hepatic bile flow and composition, and the choleretic effects of taurocholate, taurodehydrocholate, secretin, and glucagon in anesthetized puppies of 0-3 (n = 13), 7-21 (n = 9), and 28-42 (n = 8) days of age, and in fed (n = 4) and fasted (n = 4) adult dogs. Although gallbladder bile volume was similar in all puppies, chloride concentration in gallbladder bile declined with age (54.2, 33.2, 22.6, 15.9, and 5.8 mEq/liter in these respective groups), and so did bicarbonate concentration (43.5, 26.1, 17.6, 11.4, and 5.7 mEq/liter). In contrast, the concentrations of sodium (175.4, 189.2, 224.5, 251.6, and 279.4 mEq/liter) and bile acids (77.8, 137.3, 206.2, 219.6, and 280.7 mEq/liter) increased. Spontaneous bile flow rate in 0-to 3-day-old puppies averaged 0.194 pl/min/g and increased to 0.365 pl/min/g in puppies of 28-42 days of age. The latter value was not significantly different from that in fed adult dogs (0.344 pl/min/g). '4C-erythritol bile-toplasma ratio in spontaneously secreted bile increased with age (1.05, 1.08, 1.26, 1.48, and 1.70), and chloride concentration decreased (96.8, 85.8, 79.2, 74.3, and 60.1 mEq/ liter). The choleretic activity of taurocholate (2 pmol/min/ kg) was the same in all puppies (7.8 pI/pmol) and adult animals (7.2 pl/pmol). Taurodehydrocholate (2 pmol/min/ kg) increased bile flow by a greater magnitude, yet its choleretic activity in the puppies (13.3 pI/pmol) was the same as that in adult dogs (12.7 pl/pmol). In all animals, total bile acid excretion accounted for 70-95s of the infused taurocholate or taurodehydrocholate. Secretin (1-20 CU/kg/h) and glucagon (1-20 pg/kg/h) produced a minimal, or no effect on bile flow in 0-to 3-day-old puppies. In puppies of 28-42 days of age, the choleretic effect of these hormones was 30-45% of that seen in adult animals. These findings suggest that gallbladder and ductular bile water reabsorption, canalicular secretion, and hormone choleresis are all deficient processes in the newborn puppy and develop during postnatal life. (Pediatr Res 20: 203-208,1986) Abbreviations TC, taurocholate TDHC, taurodehydrocholate B/P, bile-to-plasma ratio

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Erythritol and mannitol clearances with taurocholate and secretin-induced cholereses.

Cited by 24 publications

References 12 publications

Choleretic effect of valproic acid in the rat

Choleretic effect of valproic acid in the rat

Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

Bile Secretion and its Control in the Newborn Puppy

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