Enteral Absorption of Erythropoietin in the Suckling Rat
| Autor: | Bohuslav Dvorak, James G. Grille, Amy L Miller-Gilbert, Suann S Woodward, Suzanne H. Dubuque, Catherine S. Williams, Pamela J. Kling, Otakar Koldovsky |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Breast milk Biology Enteral administration Rats Sprague-Dawley In vivo Internal medicine medicine Animals Humans Erythropoietin Saline Gastrointestinal tract Recombinant Proteins Animals Suckling Rats Milk Endocrinology Intestinal Absorption Pediatrics Perinatology and Child Health Erythropoiesis Female Digestion medicine.drug |
| Zdroj: | Pediatric Research. 50:261-267 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/00006450-200108000-00016 |
| Popis: | Milk contains biologically relevant concentrations of erythropoietin (Epo), the primary hormone responsible for erythrocyte production. In animals, milk-borne Epo stimulates erythropoiesis. Epo receptors have been found in nonerythropoietic tissues including gastrointestinal tract. We hypothesized that milk-borne Epo is distributed to local gastrointestinal tissues, absorbed intact, and then distributed peripherally via the systemic circulation. Rat milk protected recombinant human Epo (rhEpo) from degradation in the suckling rat gastrointestinal tract. Simulated digestion of (125)I-rhEpo in suckling rat gastrointestinal juices was performed. When measured by acid precipitation and immunoassay, rat milk protected rhEpo from gastrointestinal juices better than saline (p0.0001). The fate of enterally administered milk-borne (125)I-rhEpo was examined in 10-d-old rats. RhEpo fed in rat milk was better protected from in vivo proteolytic degradation than rhEpo in saline (p0.05). After enteral (125)I-rhEpo dosing, radiolabeled protein from gastric tissue comigrated on SDS-PAGE with intact rhEpo at 36.5 kD. To determine the local and systemic distribution of physiologic intakes of rhEpo, suckling rats were fed (125)I-rhEpo in rat milk, and tissues were harvested 1, 2, and 4 h later. Intact (125)I-rhEpo was found in gastric and small intestinal walls and lumens. Five percent of total administered dose was found intact in the plasma, whereas another 8 to 10% of total administered dose was localized to bone marrow, percentages comparable to those seen after parenteral administration. Radiolabel was also localized to liver and peripheral solid tissues. These patterns of localization and degradation of rhEpo after acute administration support both systemic absorption and gastrointestinal cellular processing. |
| Databáze: | OpenAIRE |
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