Erythropoietin protects against necrotizing enterocolitis of newborn rats by the inhibiting nitric oxide formation.
BACKGROUND
Necrotizing enterocolitis (NEC) is an important neonatal disease with a high mortality rate; erythropoietin (Epo) is a hematopoietic growth factor. Functional Epo receptors are in the fetal and postnatal small bowel and their ligands are available for binding. Excessive nitric oxide (NO) production by an isoform of NO synthase inducible by inflammatory stimuli leads to changes in vascular permeability and tissue injury. The aim of this study was to investigate NO formation in an experimental model of NEC and the possible role of NO in the protection Epo provides against NEC.


METHODS
Twenty-four Wistar albino rat pups were divided into three groups: group 1 = control; group 2 = hypoxia-reoxygenation and saline; group 3 = hypoxia-reoxygenation and recombinant human EPO (rhEpo) pretreatment. rhEpo was given 750 U/kg/week by intraperitoneal injection 3 times a week for 2 weeks. On the 15th day, hypoxia was induced by placing the pups in a 100% CO(2) chamber for 5 min. After the hypoxia period the pups were reoxygenated for 10 min with 100% O(2) and returned to their mothers. All pups were killed 4 h after the hypoxia-reoxygenation period was over. The abdomen was opened and representative samples of injured areas were taken for histopathologic examination. Then nitrite levels were determined in the intestine by Griess Reagent.


RESULTS
On histopathological examination, injury scores in group-2 animals were found to be significantly higher than in group-3 animals (p = 0.001). Significantly increased intestinal nitrite levels were found in group-2 rats compared to the rats of groups 1 and 3 (p = 0.001 and p = 0.001, respectively). There was a positive correlation between the histological findings and the intestinal nitrite levels in group-2 and -3 animals (r = 0.94, p = 0.001; r = 0.99, p = 0.001, respectively).


CONCLUSIONS
The present study demonstrates that the Epo-pretreated group had decreased levels of NO and limited mucosal necrosis in intestinal tissue samples. We believe that these results deserve further experimental studies in order to elucidate the possible effector mechanisms involved in the inhibitory relationship between Epo, NO and NEC.
Department of Pediatrics, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Abdullah
A
Kumral
Hüseyin
H
Baskin
Nuray
N
Duman
Osman
O
Yilmaz
Mansur
M
Tatli
Erdener
E
Ozer
Necati
N
Gökmen
Sermin
S
Genc
Hasan
H
Ozkan
D000818:Animals; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000209:etiology; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000737:chemistry / Q000473:pathology; D009573:Nitrites / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D009573:Nitrites; D011994:Recombinant Proteins; D004921:Erythropoietin