Related Experiment Video
Updated: May 4, 2026
The Mesenteric Lymph Duct Cannulated Rat Model: Application to the Assessment of Intestinal Lymphatic Drug Transport
Published on: March 6, 2015
Passive jejunal bile salt absorption alters the enterohepatic circulation in immature rats
G E Stahl1, M R Mascarenhas, J C Fayer
1Division of Neonatology, Hospital of the University of Pennsylvania, Philadelphia.
Insights
Passive bile salt absorption in the jejunum decreases with age, impacting enterohepatic circulation. This age-related decline in absorption and hepatic clearance may explain bile salt level differences in immature animals and human neonates.
Area of Science:
- Gastroenterology
- Developmental Biology
- Physiology
Background:
- Enterohepatic circulation is crucial for bile salt homeostasis.
- Developmental changes in passive bile salt absorption can significantly alter this circulation.
- Understanding these changes is key to explaining physiological differences in neonates.
Purpose of the Study:
- To investigate age-related changes in passive bile salt absorption in the jejunum and ileum.
- To determine how these changes affect overall bile salt homeostasis.
- To correlate findings with bile salt levels in immature mammals and human neonates.
Main Methods:
- Studied Sprague-Dawley rats at 14, 21, and 40 days of age.
- Isolated and cannulated jejunum and ileum for bolus injection or perfusion with taurocholate and a marker.
- Collected bile samples to quantify absorption and clearance rates.
Main Results:
- Passive jejunal taurocholate absorption and absorption rates decreased significantly with age.
- Total taurocholate absorption decreased, while hepatic taurocholate clearance increased with age.
- Hepatic clearance was only saturated at 14 days, indicating developmental differences.
Conclusions:
- Decreased passive jejunal bile salt absorption with age is a key finding.
- Reduced hepatic bile salt clearance in immature animals contributes to altered bile salt levels.
- These developmental changes likely explain low intraluminal and high serum bile salt levels in neonates.
Background:
Developmental changes in passive bile salt absorption may alter the enterohepatic circulation.
Methods:
14-, 21-, and 40-day-old anesthetized male Sprague-Dawley rats were studied. Jejunum and ileum were isolated, cannulated, and injected or perfused with a taurocholate, [3H]taurocholate, and nonabsorbable marker solution. Bile was collected.
Results:
Using bolus injection, jejunal taurocholate absorption rates and total taurocholate absorption were nonsaturable, linearly related to taurocholate dose, and decreased from 14 days (1.62 nmol.cm-1.min-1) to 21 days (1.05 nmol.cm-1.min-1) and 40 days (0.54 nmol.cm-1.min-1). While total taurocholate absorption decreased (14 days, 52.4%; 21 days, 43.7%; 40 days, 30.5%), hepatic taurocholate clearance increased (14 days, 18.2%; 21 days, 23.7%; 40 days, 37.3%). Hepatic taurocholate clearance was saturated only at 14 days. Using jejunal perfusion, total taurocholate absorption (14 days, 62.0%; 21 days, 43.1%; 40 days, 45.3%) and taurocholate absorption rate decreased with age (14 days, 941.13 nmol.cm-2.min-1 per micromole of taurocholate; 21 days, 411.28 nmol.cm-2.min-1 per micromole of taurocholate; 40 days, 334.50 nmol.cm-2.min-1 per micromole of taurocholate).
Conclusions:
Passive jejunal bile salt absorption and decreased hepatic bile salt clearance could account for the low intraluminal and high serum bile salt levels observed in immature animals and in human neonates.
Related Concept Videos
01:16Methods for Studying Drug Absorption: In vitro
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
01:09Methods for Studying Drug Absorption: In situ
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
01:17Hepatic Drug Excretion: Enterohepatic Cycling
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism