Role of platelet activating factor in gentamicin and cisplatin nephrotoxicity.
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.
Dos Santos
O F
OF
Nephrology Division, Escola Paulista de Medicina, São Paulo, Brasil.
Boim
M A
MA
Barros
E J
EJ
Schor
N
N
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
D004224:Diterpenes; D005839:Gentamicins; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C050422:BN 52063; C045856:ginkgolide B; D002945:Cisplatin