Bioavailability of granulocyte colony-stimulating factor administered enterally to suckling mice

JA Gersting, CA Kotto-Kome, Y Du… - Pharmacological …, 2003 - Elsevier
JA Gersting, CA Kotto-Kome, Y Du, RD Christensen, DA Calhoun
Pharmacological research, 2003Elsevier
The developing fetal and neonatal gastrointestinal (GI) tract is influenced by many growth
factors, including epidermal growth factor (EGF), insulin-like growth factor (IGF), transforming
growth factor (TGF), and erythropoietin (Epo). Granulocyte colony-stimulating factor (G-CSF),
typically regarded as a hematopoietic growth factor, might also be included because it exists
in high concentrations in amniotic fluid, colostrum, and human milk, and because
granulocyte CSF receptors (G-CSF-R) are abundantly expressed on the villous enterocytes …
The developing fetal and neonatal gastrointestinal (GI) tract is influenced by many growth factors, including epidermal growth factor (EGF), insulin-like growth factor (IGF), transforming growth factor (TGF), and erythropoietin (Epo). Granulocyte colony-stimulating factor (G-CSF), typically regarded as a hematopoietic growth factor, might also be included because it exists in high concentrations in amniotic fluid, colostrum, and human milk, and because granulocyte CSF receptors (G-CSF-R) are abundantly expressed on the villous enterocytes of the developing intestine. As a first step toward understanding whether the effects of G-CSF on the GI tract were local or systemic, we sought to determine whether recombinant human G-CSF (rhG-CSF) administered enterally to suckling mice, is absorbed into the circulation, and if so, whether the G-CSF-R is essential for this absorption. We enterally administered rhG-CSF to suckling mice, selecting a daily dose based on the amount of G-CSF normally swallowed by the fetus and neonate (3ng), or in other mice, a dose of G-CSF 100 times larger (300ng). Pups were tested at either 5–7 days of age, or at 14–16 days of age. C57BL/6×129SvJ mice were used. Some mice had a targeted null mutation in the G-CSF-R gene, producing a non-functional G-CSF-R protein. At intervals following the enteral G-CSF dosing, G-CSF concentrations in plasma were measured by specific ELISA. The bioavailability of G-CSF was invariably <1%, regardless of the dose of rhG-CSF given, the age of the pups, or whether they had a functional G-CSF-R. After enteral administration of rhG-CSF to suckling mice, only minimal quantities of G-CSF are absorbed into the circulation, and the G-CSF-R is not essential for this absorption.
Elsevier
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