title: Effect of the platelet activating factor antagonist BN52021 in rabbits: role in gentamicin nephrotoxicity.
abstract: Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including drug nephrotoxicity. Aminoglycosides are potent antibiotics but their use is limited by their nephrotoxic potential. We assumed that PAF could participate in inducing gentamicin nephrotoxicity, and we used the PAF antagonist BN52021 to test this hypothesis. We studied renal glomerular and tubular function by clearance techniques and renal histology in four groups of New Zealand male rabbits treated for 7 days with isotonic saline, BN52021, gentamicin, or gentamicin + BN52021. BN52021 alone reduced only fractional excretions (FE) of sodium and chloride, without modifying the other parameters studied. Renal histology was not altered. Gentamicin reduced glomerular filtration rate and renal plasma flow. Free water clearance was not modified. Sodium, potassium, chloride, calcium, and magnesium FEs were raised. Renal histology showed a massive and diffuse tubular necrosis. BN52021 did not modify gentamicin glomerular, tubular, or histopathological alterations. These data suggest that PAF might physiologically affect tubular function in New Zealand male rabbits, increasing sodium and chloride excretions, and in a minute manner, potassium, calcium, and magnesium excretions. Under our experimental conditions, there was no evidence for a role of PAF in gentamicin nephrotoxicity.
authors.affiliation: INSERM U13, CHU Bichat, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Hanslik
authors.forename: F
authors.initials: F
authors.lastname: Blanchet
authors.forename: D
authors.initials: D
authors.lastname: Nochy
authors.forename: E
authors.initials: E
authors.lastname: Pirotzky
authors.forename: C
authors.initials: C
authors.lastname: Guilmard
authors.forename: N
authors.initials: N
authors.lastname: Seta
authors.forename: C
authors.initials: C
authors.lastname: Carbon
mesh_terms: D000818:Animals; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000652:urine; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007279:Injections, Subcutaneous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011817:Rabbits
chemical_list: D004224:Diterpenes; D004573:Electrolytes; D005839:Gentamicins; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B