Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat kidneys.
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.
Hasan
Jamal
J
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California Irvine, Irvine, CA, United States.
Beharry
Kay D
KD
Gharraee
Zahra
Z
Stavitsky
Yuri
Y
Abad-Santos
Patricia
P
Abad-Santos
Matthew
M
Aranda
Jacob V
JV
Modanlou
Houchang D
HD
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy; D007052:Ibuprofen / Q000494:pharmacology*; D007213:Indomethacin / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013929:Thromboxane B2 / Q000378:metabolism
D011453:Prostaglandins; D000804:Angiotensin II; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D007052:Ibuprofen; D007213:Indomethacin