Biology Reference
In-Depth Information
Gastrointestinal tract
EPOR mRNA and EPOR protein have been detected in the intestinal villi of
the proximal and distal small bowel of the human fetal and neonatal gastroin-
testinal tract, but no data are reported on adults [115, 122]. EPO protein is
present in biologically relevant concentrations in amniotic fluid and mam-
malian milk,suggesting that gastrointestinal EPOR bind ingested EPO pro-
tein [123-127]. Simulated
in vitro
digestion studies give evidence that a sig-
nificant portion of milk-borne EPO is protected against proteolytic degrada-
tion. Thus, a local effect of ingested EPO in the gastrointestinal tract can be
proposed. Functional data on the local effects of systemic or enterally admin-
istered rEPO in the human gastrointestinal tract are not yet available. In rats,
EPOR has been detected in gastric mucosal cells, intestinal epithelial cells,
and intestinal and mesenteric microvascular endothelial cells [122, 128-130].
EPOR in the gastrointestinal tract are functionally intact, since
125
I-labeled
rEPO fed to neonatal rats was found in the wall of the stomach [131].
In vitro,
rEPO has mitogenic effects on rat gastric mucosal cells [128]. Moreover,
rEPO increases the healing and stimulates the migration of rat intestinal
epithelial cells without significant proliferative effects [122].
In vivo
, sys-
temic or enteral administration of rEPO to neonatal rats increases the small
intestinal length,villous surface area and villous height, as well as the ileal
crypt depth. These trophic effects are most pronounced in the ileum and
greater if rEPO is enterally applied rather than parenterally. Recombinant
EPO does not seem to change the specific activity of disaccharidases (lactase,
maltase, or sucrase) [130]. Recent data show that rEPO stimulates the prolif-
eration and microvascular tubular formation of rat intestinal mesentery
endothelial cells [129].
The effects of enterally administered rEPO on erythropoiesis have been
studied in human preterm babies and in animal (rat) models. The results are in
part contradictory and do not allow a final conclusion on the erythropoietic
effects of milk-borne EPO or enterally administered rEPO to neonatal rats.
However, it is evident that enterally administered rEPO has no erythropoietic
effect in adult rats, except when given rectally in the presence of salicylates
that improve rectal mucosal permeability [132].
In humans, a non-controlled trial feeding high dose rEPO (1,000 U/kg body
weight per day) showed increased plasma EPO concentrations in six preterm
babies, but the reticulocyte number and hematocrit levels did not change [133].
In this study rEPO was given in a non-protein-containing buffered solution
which may have significantly decreased the stability of the protein. In a con-
trolled study, addition of rEPO (600 U/kg body weight per week in three
doses) to formula in six preterm babies resulted in higher plasma EPO con-
centrations and a higher peak in reticulocytes compared with six controls, but
no increase in hemoglobin concentration was observed. A decrease in ferritin
concentrations suggested an increased iron utilization in the group fed rEPO
[134]. In neonatal rats, 5% of enterally administered
125
I-labeled rEPO was
