Involvement of platelet-activating factor in gentamicin nephrotoxicity in rats.
To assess whether platelet-activating factor (PAF) could be involved in gentamicin-induced nephrotoxicity, we studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin treatment. Administration of gentamicin resulted in a progressive increase of plasma creatinine, a drop in creatinine clearance and an increase of urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and alkaline phosphatase (AP). Rats treated with BN-52021 and injected with gentamicin showed fewer changes in plasma creatinine and creatinine clearance, but no differences in urinary excretion of NAG and AP were observed in gentamicin-treated rats. Histological examination revealed massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN-5202 1-injected animals tubular damage was markedly attenuated. Glomeruli from gentamicin-treated rats produced larger amounts of PAF than glomeruli from control rats. In addition, in the group of BN-52021- and gentamicin-treated rats, glomerular PAF production was not significantly different from that of the control group. The present results suggest a role for PAF in gentamicin-induced nephrotoxicity.
Rodriguez-Barbero
A
A
Instituto Reina Sofia de Investigacion Nefrologica, Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, Espana.
López-Novoa
J M
JM
Arévalo
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D004224:Diterpenes; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005839:Gentamicins / Q000493:pharmacokinetics / Q000633:toxicity*; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007444:Inulin / Q000493:pharmacokinetics; D007672:Kidney Cortex / Q000473:pathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007783:Lactones / Q000494:pharmacology; D008854:Microscopy, Electron; D009336:Necrosis; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D004224:Diterpenes; D005343:Fibrinolytic Agents; D005839:Gentamicins; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D007444:Inulin; C045856:ginkgolide B