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Preventive effect of platelet-activating factor antagonist, Y-24180, against cyclosporine-induced acute

A Kawaguchi1, K Sugimoto, A Fujimura

  • 1Department of Clinical Pharmacology, Jichi Medical School, Kawachi-gun, Tochigi, Japan.

Life Sciences
|March 3, 2001
PubMed

Insights

Platelet-activating factor (PAF) receptor antagonist Y-24180 shows preventive effects against cyclosporine A (CsA)-induced acute renal failure. This suggests PAF involvement in CsA-induced renal vasoconstriction and nephrotoxicity.

Area of Science:

  • Nephrology
  • Pharmacology
  • Renal Physiology

Background:

  • Cyclosporine A (CsA) is a widely used immunosuppressant with known nephrotoxic effects.
  • Acute renal failure is a significant complication of CsA therapy.
  • The role of platelet-activating factor (PAF) in CsA-induced nephrotoxicity requires further elucidation.

Purpose of the Study:

  • To investigate the protective effect of Y-24180, a PAF receptor antagonist, against CsA-induced acute renal failure.
  • To assess the impact of Y-24180 on renal hemodynamics during CsA treatment.
  • To explore the potential involvement of PAF and endothelin-1 (Et) in CsA nephrotoxicity.

Main Methods:

  • Male Wistar rats were pretreated with Y-24180 before CsA administration.
  • Renal hemodynamics, including inulin and p-aminohippuric acid (PAH) clearances and renal vascular resistance (RVR), were measured.
  • Serum concentrations of endothelin-1 (Et) and thromboxane B2 (TxB2) were analyzed.

Main Results:

  • CsA induced a dose-dependent decrease in inulin and PAH clearances and increased RVR.
  • Y-24180 pretreatment attenuated CsA-induced reductions in PAH clearance and RVR in a dose-dependent manner.
  • Elevated serum Et concentrations were observed in CsA-treated rats, correlating significantly with RVR, while TxB2 levels remained unchanged.

Conclusions:

  • Y-24180 demonstrates a preventive effect against CsA-induced acute renal failure.
  • Platelet-activating factor (PAF) appears to play a partial role in CsA-induced renal vasoconstriction.
  • Endothelin-1 contributes to CsA-induced acute nephrotoxicity.

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