Nephrotoxicity of cyclosporine: The role of platelet‐activating factor and thromboxane

• Published in: Lipids Vol. 26; no. 12Part2; pp. 1320 - 1323
• Main Authors: Pavão dos Santos, Oscar F., Boim, Mirian A., Barros, Elvino J. G., Pirotzky, Eduardo, Braquet, Pierre, Schor, Nestor
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Berlin/Heidelberg Springer‐Verlag 01.12.1991; Springer
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Cyclosporine - toxicity; Drug toxicity and drugs side effects treatment; Glomerular Filtration Rate - drug effects; Imidazoles - pharmacology; Kidney - drug effects; Kidney - pathology; Kidney - physiology; Male; Medical sciences; Pharmacology. Drug treatments; Platelet Activating Factor - pharmacology; Platelet Activating Factor - physiology; Rats; Rats, Inbred Strains; Reference Values; Renal Circulation - drug effects; Thromboxane A2 - physiology; Thromboxane-A Synthase - antagonists & inhibitors; Toxicity: urogenital system
• DOI: 10.1007/BF02536557
• ISSN: 0024-4201

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.