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Sequestration of 3H-vitamin D3 by the fetal and neonatal rat liver
Insights
The fetal rat liver can sequester 3H-D3. Uptake decreases after birth but dramatically increases by day 22, reaching adult levels.
Area of Science:
- Hepatology
- Developmental Biology
- Pharmacokinetics
Background:
- The liver's capacity to sequester substances changes significantly during development.
- Understanding fetal and neonatal liver uptake is crucial for drug development and administration.
Purpose of the Study:
- To investigate the uptake of 3H-D3 by the fetal and neonatal rat liver.
- To characterize the developmental changes in hepatic sequestration of 3H-D3.
Main Methods:
- Tracer dose of 3H-D3 administered via umbilical vein (fetuses) or portal vein (neonates).
- 14C-sucrose used as an extracellular marker to determine sequestration.
- Uptake evaluated in fetuses and pups at various ages (3, 7, 14, 22 days).
Main Results:
- Fetal rat liver demonstrated significant 3H-D3 sequestration (11.3%).
- Neonatal uptake was initially low (3.3% at 3 days) but increased with age.
- A significant decrease in uptake occurred in the first two weeks postpartum, followed by a six-fold increase by day 22.
Conclusions:
- The fetal rat liver is capable of sequestering 3H-D3.
- Hepatic sequestration of 3H-D3 undergoes dynamic changes during the perinatal period.
- Uptake capacity in 22-day-old rats approaches that of adult rats.
Abstract:
19- to 21-day-old fetuses as well as 3-, 7-, 14-, and 22-day-old pups were used to evaluate the sequestration of a tracer dose of 3H-D3 by the fetal and neonatal rat liver. In fetuses, 3H-D3 was injected directly into the umbilical vein; in neonates, 3H-D3 was injected into the portal vein. In both cases, 14C-sucrose was used as extracellular marker. 3H-D3 sequestration was evaluated at 11.3 +/- 1.1% (means +/- SEM) in fetuses, 3.3 +/- 0.6, 4.9 +/- 0.6, 6.3 +/- 0.5 0.5 and 42.0 +/- 1.9% of the dose administered in 3-, 7-, 14-, and 22-day-old rats, respectively. These results clearly show that, in the rat, the fetal liver can take up 3H-D3. Moreover, when compared to the values obtained in the late fetal period, 3H-D3 uptake decreased significantly during the first 2 weeks post partum (p less than 0.0001) and then dramatically increased (6-fold, p less than 0.0001) between days 14 and 22 post partum, when it reached an uptake capacity similar to that previously observed in adult rats.