Indomethacin, dexamethasone, and intestinal damage in infant rats.

Abstract:

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.

authors

Patel MR,DeMarco VG,Clare-Salzler M,Li YY,Neu J

doi

10.1097/00005176-200208000-00010

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

154-61

issue

2

eissn

0277-2116

issn

1536-4801

journal_volume

35

pub_type

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