title: Gentamicin administered during gestation alters glomerular basement membrane development.
abstract: Gentamicin during gestation alters glomerular basement membrane development. A drug-induced nephrotoxicity was described for neonates after gentamicin was given intraperitoneally to pregnant Wistar rats; glomerular alterations and changes in permselectivity were important. We investigated the ultrastructure of the glomerular basement membrane (GBM), the arrangement of anionic sites, and the urinary proteins at two ages, with 1-day- and 12-month-old control and prenatally exposed animals. For neonates, the pattern of glomerular differentiation was similar, anionic sites were made of heparan sulfate proteoglycans, and the GBM had the same total thickness in both groups. After transplacental gentamicin exposure, the lamina densa was larger; the laminae rarae were thinner; the density of anionic sites was increased; the levels of hydroxyproline, sulfate, and hexuronic acid in the kidney were increased; and the immunoelectrophoresis of urinary proteins was abnormal. For adults, prenatal exposure to gentamicin led to altered juxta-medullary glomeruli with a larger GBM and abundant anionic sites, especially in the lamina densa, and to a protein excretion different from that of controls. Thus, gentamicin administered during pregnancy leads to permanent alterations of the GBM with modifications of both the layers and the anionic sites, possibly because of a perturbed protein metabolism. These altered glomeruli are at risk during life and could be the starting point for a kidney disease.
authors.affiliation: Laboratoire de Biologie Cellulaire, Université de Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Smaoui
authors.forename: J P
authors.initials: JP
authors.lastname: Mallie
authors.forename: M
authors.initials: M
authors.lastname: Schaeverbeke
authors.forename: A
authors.initials: A
authors.lastname: Robert
authors.forename: J
authors.initials: J
authors.lastname: Schaeverbeke
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D001485:Basement Membrane / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D001665:Binding Sites; D002463:Cell Membrane Permeability; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000196:embryology* / Q000254:growth & development; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000838:Anions; D005839:Gentamicins