title: Role of platelet activating factor in gentamicin and cisplatin nephrotoxicity.
abstract: The present study was undertaken to evaluate the effects of platelet activating factor (PAF) antagonists on nephrotoxicity induced by gentamicin (GENTA) and cisplatin (DDP) in rats. PAF infusion provoked a 56% decline in single nephron (SN) GFR due to a decrease in glomerular plasma flow (QA, 55%), glomerular transcapillary hydraulic pressure (delta P, 13%), and glomerular ultrafiltration coefficient (Kf, 37%). Four days after a single dose of DDP (6 mg/kg, i.p.) we observed non-oliguric acute renal failure (ARF) with reduced SNGFR (45%), QA (46%) and delta P (10%) and unchanged Kf. GENTA administration for 10 days (40 mg/kg, i.p. daily) induced a decline in SNGFR (40%), QA (41%) and Kf (41%). Chronic treatment with a GENTA + PAF antagonist (BN 52021) partially prevented the decline in SNGFR (22%) by an amelioration in QA (25%) and Kf (13%). However, simultaneous treatment with DDP and BN 52063 completely prevented the ARF induced by DDP, normalizing all parameters of renal function. Thus, PAF may be a potential mediator involved in the nephrotoxicity induced by GENTA and DDP.
authors.affiliation: Nephrology Division, Escola Paulista de Medicina, São Paulo, Brasil.
authors.forename: O F
authors.initials: OF
authors.lastname: Dos Santos
authors.forename: M A
authors.initials: MA
authors.lastname: Boim
authors.forename: E J
authors.initials: EJ
authors.lastname: Barros
authors.forename: N
authors.initials: N
authors.lastname: Schor
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004224:Diterpenes; D005839:Gentamicins / Q000633:toxicity*; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004224:Diterpenes; D005839:Gentamicins; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C050422:BN 52063; C045856:ginkgolide B; D002945:Cisplatin