Enteral erythropoietin and iron stimulate erythropoiesis in suckling rats

J Pediatr Gastroenterol Nutr. 2008 Feb;46(2):202-7. doi: 10.1097/MPG.0b013e3181559e8b.

Abstract

Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Suckling
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Duodenum / drug effects
  • Duodenum / growth & development
  • Enteral Nutrition*
  • Erythrocyte Indices
  • Erythropoiesis / drug effects*
  • Erythropoiesis / physiology
  • Erythropoietin / administration & dosage*
  • Erythropoietin / pharmacology
  • Gastrostomy
  • Hemoglobins / analysis
  • Humans
  • Infant, Newborn
  • Infant, Premature / growth & development
  • Infant, Premature, Diseases / drug therapy
  • Iron, Dietary / administration & dosage*
  • Iron, Dietary / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins

Substances

  • Hemoglobins
  • Iron, Dietary
  • Recombinant Proteins
  • Erythropoietin