Gut 2001;49:182-189 ( August )

Article

Erythropoietin acts as a trophic factor in neonatal rat intestine S E Juul^a, D J Ledbetter^b, A E Joyce^a, C Dame^a, R D Christensen^a, Y Zhao^a, V DeMarco^a

^a Department of Pediatrics, University of Florida College of Medicine, Florida, USA, ^b Department of Surgery, University of Florida College of Medicine, Florida, USA

Correspondence to: Dr S Juul, Division of Neonatology, University of Washington, PO Box 356320, Seattle, Washington 98195, USA. sjuul{at}u.washington.edu

Accepted for publication 29 January 2001

BACKGROUNDErythropoietin (Epo) receptors are present on enterocytes of fetal and neonatal small bowel but the role of Epo in the bowel is not known.
AIMSWe tested the following hypotheses: (1) enterally dosed Epo is absorbed from the intestines of neonatal rats, (2) Epo acts as a trophic factor in developing small bowel, and (3) the trophic effects of Epo are dependant on the route of administration.
METHODSThe dose dependant effects of enterally dosed recombinant human erythropoietin (rEpo 0-1000 U/kg/day) were studied in artificially raised rat pups and compared with dam raised controls and dam raised pups given rEpo in rat milk. After one week, reticulocyte counts, haematocrits, and plasma Epo concentrations were measured, and calibrated morphometric measurements of villi were performed. The effects of route of rEpo administration (enteral v parenteral) on erythropoiesis, bowel growth, and disaccharidase activity were studied in nursing pups treated for one and two weeks.
RESULTSSerum Epo concentrations ranged from undetectable (<0.6 mU/ml) to 8.4 mU/ml in control and enterally dosed pups (median 1.8 mU/ml), and from 4.9 to 82.3 mU/ml (median 20.4 mU/ml) in parenterally dosed animals. No increase in haematocrit or reticulocyte count was noted in enterally treated pups compared with controls after up to two weeks of treatment. Small bowel length was greater in rEpo treated pups, and a dose dependent increase in villus surface area which was independent of the route of dosing and associated with increased BrdU uptake was found.
CONCLUSIONSrEpo is not enterally absorbed in an intact and functional form from the intestines of neonatal rat pups. Thus enterally dosed rEpo has no erythropoietic effects. However, rEpo acts as a trophic factor in developing rat small bowel whether given enterally or parenterally.


Keywords: erythropoietin; enterocytes; breast milk; development; neonate; rat

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© 2001 by Gut
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