Related Experiment Video
Updated: Jul 9, 2026
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat kidneys
Jamal Hasan1, Kay D Beharry, Zahra Gharraee
1Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California Irvine, Irvine, CA, United States.
Insights
Early ibuprofen use in neonatal rats showed fewer adverse renal effects than indomethacin. Indomethacin suppressed key renal prostanoids and COX-2, impacting kidney development and function long-term.
Area of Science:
- Neonatal pharmacology
- Renal physiology
- Prostanoid signaling
Background:
- Patent ductus arteriosus (PDA) in preterm infants often treated with indomethacin.
- Indomethacin is linked to renal dysfunction; ibuprofen offers similar efficacy with fewer renal side effects.
- The differential impact of early postnatal indomethacin versus ibuprofen on neonatal kidney function requires further investigation.
Purpose of the Study:
- To compare the effects of early postnatal ibuprofen and indomethacin on neonatal rat renal prostanoids, COX-2 expression, and angiotensin II.
- To determine if ibuprofen has less adverse effects on renal function compared to indomethacin in early development.
Main Methods:
- Newborn rats received daily intraperitoneal injections of therapeutic doses of ibuprofen or indomethacin for the first three days of life.
- Control rats received saline injections.
- Kidneys were analyzed in suckling and weanling rats for prostanoid levels (PGE2, PGF2α, 6-ketoPGF1α, TxB2), COX-2 expression, and angiotensin II concentrations.
Main Results:
- Indomethacin suppressed PGE2 and COX-2 expression while increasing PGF2α in suckling rats.
- Ibuprofen increased COX-2 and angiotensin II levels in suckling rats.
- Both drugs reduced 6-ketoPGF1α and TxB2, but indomethacin's suppressive effect was sustained into the weanling stage.
Conclusions:
- Indomethacin has more potent, long-lasting suppressive effects on renal COX-2 and vasodilator prostanoids compared to ibuprofen.
- These sustained effects of indomethacin may contribute to its more severe adverse renal effects during early postnatal development.
- Ibuprofen appears to be a safer alternative regarding renal prostanoid regulation in neonatal development.
Abstract:
The use of indomethacin in preterm newborn infants with symptomatic patent ductus arteriosus is associated with compromised renal function. Ibuprofen has been shown to be as effective as indomethacin with fewer renal side effects. We examined the hypothesis that early postnatal ibuprofen has less adverse effects on neonatal rat renal prostanoids, COX-2 expression, and angiotensin II than indomethacin. Newborn rats received IP injections of human therapeutic doses of ibuprofen or indomethacin on the first 3 days of life. Control rats were treated with equivalent volume saline. Kidneys were assessed in suckling and weanling rats for prostanoids, COX-2 expression, and angiotensin II. In suckling rats, indomethacin suppressed PGE(2) and COX-2 expression, and increased PGF(2alpha), whereas ibuprofen increased COX-2 and angiotensin II. Although both NSAIDs suppressed 6-ketoPGF(1alpha) and TxB(2) levels in suckling rats, the effect was sustained in weanling rats with indomethacin. Our findings demonstrate that indomethacin exhibits more potent suppressive effects on renal COX-2 and vasodilator prostanoids which are important regulators of renal development and function. These long-term, sustained effects may explain in part, why indomethacin exerts more severe adverse renal effects than ibuprofen, when administered during early postnatal life.
