title: Effects of ibuprofen treatment on the developing preterm baboon kidney.
abstract: Preterm neonates are commonly exposed postnatally to pharmacological treatments for a patent ductus arteriosus. Exposure of the developing kidney to nephrotoxic medications may adversely impact renal development. This study aimed to determine the effect of early postnatal ibuprofen treatment, both alone and in combination with a nitric oxide synthase inhibitor (NOSi), on renal development and morphology. Baboon neonates were delivered prematurely at 125-day (125d) gestation (term = 185d) and were euthanized at birth or postnatal day 6. Neonates were divided into four groups: 125d gestational controls (n = 8), Untreated (n = 8), Ibuprofen (n = 6), and ibuprofen (Ibu)+NOSi (n = 4). Animals in the Ibuprofen and Ibu+NOSi groups received five doses of ibuprofen, with the Ibuprofen+NOSi animals additionally administered a NOS inhibitor (N(G)-monomethyl-l-arginine). There was no difference among groups in body weight, kidney weight, or glomerular generation number. Nephrogenic zone width was significantly reduced in the Ibuprofen group (123.5 ± 7.4 μm) compared with the 125d gestational control (176.1 ± 6.9 μm) and Untreated animals (169.7 ± 78.8 μm). In the Ibu+NOSi group, nephrogenic zone width averaged 152.7 ± 3.9 μm, which was not significantly different from any other group. Morphologically abnormal glomeruli were present at a range of 0.0-22.9% in the Untreated group, 0.0-6.1% in the Ibuprofen group, and 0.0-1.4% in the Ibu+NOSi group. In conclusion, early postnatal ibuprofen exposure is associated with a reduced nephrogenic zone width, which may suggest the early cessation of nephrogenesis following treatment. Ultimately, this may impact the number of nephrons formed in the preterm kidney.
authors.affiliation: Dept. of Anatomy and Developmental Biology, Bldg. 76, Monash Univ., Clayton, Victoria, Australia, 3800.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Sutherland
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Yoder
authors.forename: Donald
authors.initials: D
authors.lastname: McCurnin
authors.forename: Steven
authors.initials: S
authors.lastname: Seidner
authors.forename: Lina
authors.initials: L
authors.lastname: Gubhaju
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Clyman
authors.forename: M Jane
authors.initials: MJ
authors.lastname: Black
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000502:physiology; D004347:Drug Interactions; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007052:Ibuprofen / Q000633:toxicity*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects; D009399:Nephrons / Q000166:cytology / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D010215:Papio; D011247:Pregnancy; D047928:Premature Birth; D014556:Urine; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D007052:Ibuprofen