Nephrotoxicity of cyclosporine: the role of platelet-activating factor and thromboxane.
Cyclosporine (CsA), an immunosuppressive agent, is potentially nephrotoxic. We had previously observed that acute administration of CsA to Munich-Wistar rats induced a decrease in single nephron glomerular filtration rate, due to a decline in glomerular plasma flow, and in the glomerular ultrafiltration coefficient. Moreover, these alterations were prevented when an antagonist of platelet-activating factor (PAF) was administered. In the present study we examined whether the protective effect of the PAF blocker in CsA nephrotoxicity could have been mediated by thromboxane (TxA2). Our data show that the PAF effects were not mediated by TxA2, since administration of dazmegrel, a thromboxane synthetase inhibitor, did not ameliorate the acute renal failure caused by CsA. Thus, PAF appears to be a direct mediator of acute CsA nephrotoxicity, while TxA2 is not significantly involved in this process.
dos Santos
O F
OF
Nephrology Division, Escola Paulista de Medicina, São Paulo, Brazil.
Boim
M A
MA
Barros
E J
EJ
Pirotzky
E
E
Braquet
P
P
Schor
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D016572:Cyclosporine / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D010972:Platelet Activating Factor; C039242:dazmegrel; D013928:Thromboxane A2; D016572:Cyclosporine; D013930:Thromboxane-A Synthase