Indomethacin, dexamethasone, and intestinal damage in infant rats.
BACKGROUND
Indomethacin is commonly used in the Neonatal Intensive Care Unit to induce closure of the patent ductus arteriosus and to prevent intraventricular hemorrhage. It is known that indomethacin causes intestinal ulceration in adults, but its effect in infants is less clear. In a preliminary experiment, it was found that the administration of 10 mg/kg/d of indomethacin, a dose that damages the adult rat intestine, had no detrimental effects on newborn suckling rats whereas dexamethasone at 0.25 mg/kg/d caused significant growth failure and villous blunting. It was then hypothesized that the lack of intestinal damage with indomethacin in infants was related to protection given by mother's milk.


METHODS
Subsequent experiments were performed wherein 10 mg/kg/d of indomethacin was provided to infant mother-reared, infant artificially fed, and adult rats. The expression of intestinal cyclooxygenases in the prostaglandin synthetic pathway of control rats was examined to initiate an exploration into a mechanism for the developmental response to indomethacin.


RESULTS
Mother-reared and artificially fed infant rats demonstrated resistance to the ulcerogenic effects of indomethacin, in contrast to the adults. A differential presence of cyclooxygenase-1 and cyclooxygenase-2 was not distinctly seen between infancy and adulthood.


CONCLUSIONS
The results indicate that a varying response to the damaging effects of indomethacin on the intestine occurs during development with the infant being less susceptible than the adult. This differed from the effects of dexamethasone administration, which caused significant intestinal atrophy in the infant rats. The intestinal protection to the effects of indomethacin in infants is not dependent on mother's milk or a developmental difference in the prostaglandin biosynthetic pathway.
Division of Neonatology, Department of Pediatrics, J Hillis Miller Health Center, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Manish R
MR
Patel
Vincent G
VG
DeMarco
Michael
M
Clare-Salzler
Yi Yu
YY
Li
Josef
J
Neu
D000367:Age Factors; D000818:Animals; D000833:Animals, Suckling; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D005526:Food, Formulated; D007213:Indomethacin / Q000009:adverse effects*; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008297:Male; D008892:Milk / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014456:Ulcer / Q000139:chemically induced* / Q000473:pathology
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin