Enteral erythropoietin and iron stimulate erythropoiesis in suckling rats.
OBJECTIVE
A primary objective was to evaluate whether addition of enteral iron supplementation will facilitate a systemic erythropoietic effect when feeding erythropoietin (Epo) to suckling rats. A secondary objective was to confirm that iron does not alter the previous finding that enteral Epo exerts local trophic effects on the small intestine.


METHODS
Four-day-old Sprague-Dawley rats underwent gastrostomy and were fed a cow's milk-based rat milk substitute for 8 days. We studied rats fed rat milk substitute alone (control), enteral Epo 425 U x kg(-1) x day(-1), and enteral Epo 1700 U x kg(-1) x day(-1), and the effects of oral iron sulfate (Fe) therapy (6 mg x kg(-1) x day(-1)). Blood was collected to measure hemoglobin (Hb), reticulocytes, red cell indices, and zinc protoporphyrin/heme. To confirm previous work describing trophic effects of enteral Epo on the intestine, duodenal villous height was measured.


RESULTS
Hb levels in control (84 +/- 1 g/L) were similar to Epo 425 (87 +/- 1 g/L). Hb levels in control+Fe (97 +/- 1 g/L), Epo 425+Fe (97 +/- 1 g/L), and Epo 1700 (94 +/- 1 g/L) were higher than control, P < 0.001, but mean Hb level in Epo 1700+Fe was higher (105 +/- 1 g/L) than the other groups, P < 0.003. Mean cell volume was higher in rats receiving iron supplementation, compared with those without iron, P < 0.005. Duodenal villous height was taller in Epo 1700+Fe compared with control + Fe, P < 0.01.


CONCLUSIONS
If combined with sufficient iron supplementation, high-dose Epo artificially fed to suckling rats exerted a systemic erythropoietic effect in addition to the previously reported local trophic effects.
Kling
Pamela J
PJ
University of Wisconsin and Meriter Hospital, Department of Pediatrics, 6 Center, 202 S Park Street, Madison, WI 53715, USA. pkling@facstaff.wisc.edu
Willeitner
Andrea
A
Dvorak
Bohuslav
B
Blohowiak
Sharon E
SE
D000818:Animals; D000833:Animals, Suckling; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004386:Duodenum / Q000187:drug effects / Q000254:growth & development; D004750:Enteral Nutrition; D004909:Erythrocyte Indices; D004920:Erythropoiesis / Q000187:drug effects* / Q000502:physiology; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology; D005774:Gastrostomy; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development; D007235:Infant, Premature, Diseases / Q000188:drug therapy; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D006454:Hemoglobins; D019266:Iron, Dietary; D011994:Recombinant Proteins; D004921:Erythropoietin