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Role of platelet activating factor in gentamicin and cisplatin nephrotoxicity
O F Dos Santos1, M A Boim, E J Barros
1Nephrology Division, Escola Paulista de Medicina, São Paulo, Brasil.
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.
Insights
Platelet activating factor (PAF) antagonists partially protected against gentamicin nephrotoxicity and fully prevented cisplatin-induced acute renal failure in rats, suggesting PAF
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Gentamicin (GENTA) and cisplatin (DDP) are nephrotoxic drugs.
- Platelet activating factor (PAF) plays a role in renal injury.
Purpose of the Study:
- To investigate the protective effects of PAF antagonists against GENTA and DDP-induced nephrotoxicity in rats.
- To elucidate the role of PAF in drug-induced kidney injury.
Main Methods:
- Rats were treated with GENTA or DDP to induce nephrotoxicity.
- PAF antagonists (BN 52021 and BN 52063) were administered concurrently or chronically.
- Single nephron glomerular filtration rate (SNGFR) and its determinants (glomerular plasma flow, hydraulic pressure, ultrafiltration coefficient) were measured.
Main Results:
- GENTA induced a significant decline in SNGFR, glomerular plasma flow, and ultrafiltration coefficient.
- DDP caused acute renal failure with reduced SNGFR and glomerular plasma flow.
- PAF antagonists partially ameliorated GENTA nephrotoxicity and completely prevented DDP-induced acute renal failure.
Conclusions:
- PAF is implicated as a mediator in gentamicin and cisplatin-induced nephrotoxicity.
- PAF antagonists demonstrate potential therapeutic value in mitigating drug-induced kidney injury.