Hormonal influences of early postnatal indomethacin and ibuprofen in neonatal rats.
OBJECTIVE
Indomethacin and ibuprofen are administered to preterm neonates for symptomatic patent ductus arteriosus. The drugs suppress prostaglandins (PGs) which modulate growth and secretion of various hormones. We examined the hypothesis that early postnatal indomethacin and ibuprofen influence growth and GH-IGF-I-insulin and HPA axes in neonatal rats.


METHODS
Rat pups received IP injections of saline (Sal) on P1, P2, and P3; 10mg/kg ibuprofen on P1 followed by 5mg/kg on P2 and P3; or 0.2mg/kg indomethacin on P1 followed by 0.1mg/kg on P2 and P3. Serum and hepatic GH, GHBP and IGF-I; and serum corticosterone and insulin levels were determined.


RESULTS
Ibuprofen suppressed somatic growth in the sucking rats, but the effect was transient, resolving by P14. Indomethacin had an opposite, latent effect on body weight and liver to body weight ratios in weanling rats. Both indomethacin and ibuprofen had profound hormonal effects that differed in magnitude and timing. Indomethacin resulted in a sustained elevation in corticosterone levels at P21, while ibuprofen increased serum and hepatic GH levels. Both drugs suppressed GHBP in serum at P7 and P14; and liver at P4 and P7, but a rebound increase in serum GHBP was noted at P21 with Ibuprofen only. Both drugs increased serum IGF-I at P7. The effect remained sustained with indomethacin.


CONCLUSIONS
These results provide evidence for an involvement of PGs in the regulation of growth as well as the GH-IGF and HPA axes. Therefore, early postnatal exposure to PG inhibitors may further exacerbate postnatal growth restriction and ability to cope with stress.
Gebrekristos
Bisrat
B
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California, Irvine, CA 92868, United States.
Beharry
Kay D
KD
Brock
Romy S
RS
Kuniyoshi
Katherine
K
Abad-Santos
Patricia
P
Abad-Santos
Matthew
M
Aranda
Jacob V
JV
Modanlou
Houchang D
HD
D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000097:blood; D003345:Corticosterone / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D013006:Growth Hormone / Q000037:antagonists & inhibitors* / Q000097:blood; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects*; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000172:deficiency; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D016861:Cyclooxygenase Inhibitors; D007328:Insulin; D011453:Prostaglandins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein; D003345:Corticosterone; D007052:Ibuprofen; D007213:Indomethacin