Hormonal influences of early postnatal indomethacin and ibuprofen in neonatal rats

Abstract

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. Design Rat pups received IP injections of saline (Sal) on P1, P2, and P3; 10 mg/kg ibuprofen on P1 followed by 5 mg/kg on P2 and P3; or 0.2 mg/kg indomethacin on P1 followed by 0.1 mg/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.