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Indian Pediatr 2010;47: 887-888 |
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Effects of Enteral Insulin on Hypoxic Changes
in a Rat Model of Necrotizing Enterocolitis |
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Begum Yurdakok, Fuat Emre Canpolat
*#,
Diclehan Orhan* and Gulsev Kale*
From the Department of Pharmacology and Toxicology,
Ankara University Faculty of Veterinary Medicine;
and *Department of Pediatrics, Faculty of Medicine, Hacettepe University,
Ankara, Turkey.
Correspondence to:
[email protected]
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The aim of this study was to determine if oral administration of insulin
would protect intestinal cell damage in a hypoxia-induced experimental
NEC model in rats. Rats were subjected to hypoxia-reoxygenation and then
were returned to standard conditions, other were treated with insulin.
According to our results, oral insulin does not prevent mild
intestinal mucosal changes during hypoxic injury in rats.
Key words: Hypoxia, Insulin, Necrotizing enterocolitis.
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N
ecrotizing enterocolitis (NEC) in
preterm infants is characterized by various degrees of mucosal or
transmural necrosis of the intestinal tissue, and is a major cause of
morbidity and mortality(1). Experimental studies have suggested that both
insulin-like growth factor I (IGF-I) and II (IGF-II) are involved in
modulation of growth and differentiation of normal small bowel(2) and
protection of intestinal mucosa from hypoxia and apoptosis(3,4). Low serum
IGF-I values were also found to be correlated with NEC in preterm
infants(5). Beneficial effects of oral insulin on intestinal recovery
following ischemia-reperfusion injury have been shown in rat(6). The
purpose of this study was to determine whether enteral insulin protects
intestinal cells from hypoxia induced NEC in an animal model.
Hypoxia was accomplished by placing the pups in an
airtight Plexiglas (Rohm & Haas, Philadelphia, PA) chamber (Vacunit;
Echmann, England), which was perfused with 100% CO 2
for five minutes. Following hypoxia, the animals were reoxygenated for
five minutes with 100% oxygen. Group 1 (untreated, n=9) rats served
as untreated control group after hypoxia-reoxygenation. Group 2 (insulin
treated, n=11) were subjected to hypoxia-reoxygenation (HO), and
were treated with enteral insulin (Humulin, Lilly, Fegersheim, France)
beginning 15-20 minutes following HO, and given by orogastric route once a
day at a dose of 10 U/kg body weight for five days. Representative 1 cm
long specimens were taken for histological study from duodenum, proximal,
mid and distal small intestine, proximal and distal colon. All seven
histological sites were calculated for each case and a mean result was
compared. The specimens were dehydrated and embedded in paraffin wax using
standart techniques and sections were stained with hematoxylin and eosin.
Samples were taken randomly from each specimen (seven part of one case)
and graded microscopically in a blinded fashion on a scale from 0 to 4
according to grading system proposed by Clark, et al.(7).
The lesions in the untreated rats had similar
histopathologic findings as seen in neonatal NEC, but intestinal damages
were not severe. Intestinal injury median score was 0.39 (range 0.33-0.66)
in the untreated group. Insulin treated group had a median score of 0.44
(range 0-0.66) (P=0.50).
Intestinal ischemia and the effects of hypoxia have
been studied by several animal models. Hypoxia is associated with
decreased mucosal blood flow and mucosal ischemic changes in neonatal
rats(8). In another animal trial, enteral administration of insulin led to
a higher lactase activity and less feed intolerance(6).
We conclude that insulin does not reduce hypoxic
changes on the intestines in an experimental model of NEC. Further animal
studies are needed to clarify protective effect of insulin on more severe
intestinal damage during experimental NEC as well as with higher doses of
insulin.
Funding and Competing interests: None.
References
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2006; 368: 1271-1283.
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A, et al. Insulin like growth factor attenuates apoptosis and
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