title: Indomethacin, ibuprofen and gentamicin administered during late stages of glomerulogenesis do not reduce glomerular number at 14 days of age in the neonatal rat.
abstract: Premature neonates are frequently administered indomethacin, ibuprofen and gentamicin during the period of active glomerulogenesis. These drugs are known to have nephrotoxic effects, but the morphological effect of these drugs is unknown. The purpose of this study was to determine whether administration of these drugs during the late stages of glomerulogenesis in the rat has an effect on glomerular endowment. Rat pups were given, intraperitoneally, indomethacin, ibuprofen or indomethacin and gentamicin for the first 5 days of their postnatal life. The pups were killed at 14 days of age at completion of glomerulogenesis. The total number of glomeruli in the left kidney was determined by the physical disector/fractionator stereological technique. There was no difference between treatment groups in total number of glomeruli per kidney (P = 0.45). There were significantly fewer glomeruli per gram of kidney in those rat pups that had received indomethacin or ibuprofen (P < 0.0001). The reduction in the number of glomeruli per gram of kidney may indicate augmented growth of nephron tubules and/or collecting ducts, and/or be a consequence of oedema secondary to drug exposure. Further study is required to determine whether reduced glomerular number is seen in older animals or following exposure to these drugs at different time-points in kidney development.
authors.affiliation: Department of Neonatology, The Canberra Hospital, P.O. Box 11, Woden, ACT, 2606, Australia. alison.kent@act.gov.au
authors.forename: Alison L
authors.initials: AL
authors.lastname: Kent
authors.forename: Rebecca
authors.initials: R
authors.lastname: Douglas-Denton
authors.forename: Bruce
authors.initials: B
authors.lastname: Shadbolt
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dahlstrom
authors.forename: Lesley E
authors.initials: LE
authors.lastname: Maxwell
authors.forename: Mark E
authors.initials: ME
authors.lastname: Koina
authors.forename: Michael C
authors.initials: MC
authors.lastname: Falk
authors.forename: David
authors.initials: D
authors.lastname: Willenborg
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology; D004338:Drug Combinations; D005260:Female; D005839:Gentamicins / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000254:growth & development*; D009399:Nephrons / Q000254:growth & development*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018712:Analgesics, Non-Narcotic; D000900:Anti-Bacterial Agents; D002317:Cardiovascular Agents; D004338:Drug Combinations; D005839:Gentamicins; D007052:Ibuprofen; D007213:Indomethacin