Protective effect of UR-12670 on chronic nephropathy induced by warm ischaemia in ageing uninephrectomized rats.

Abstract

BACKGROUND:

In young animals, renal ischaemia/reperfusion injury and mass reduction are associated with chronic lesions that mimic those found in chronic rejection. We have shown that the phospholipid platelet-activating factor (PAF) participates in young animals in such chronic nephropathy. Here we examine the long-term effects of the orally active PAF antagonist, UR-12670 in ageing uninephrectomized rats exposed to prolonged warm ischaemia.

METHODS:

Fifteen- to eighteen-month-old uninephrectomized male Sprague-Dawley rats were allocated into three groups and followed for 16 weeks: UNx, rats without ischaemia; UNxISC, ischaemic kidney (60 min), and UNxISC+UR, ischaemic kidney and UR-12670 from day 0 to the 16th week. Serum creatinine and proteinuria were monitored every 4 weeks. At the end of the study, conventional histology was performed and monocyte-macrophages were identified with the specific monoclonal antibody ED-1.

RESULTS:

The UNxISC group had severe acute renal failure with a high mortality rate, which was associated with incomplete restoration of renal function. Renal insufficiency in this group was sustained throughout the follow-up. Both UNx and UNxISC groups developed progressive proteinuria from the 12th week. Though UNxISC+UR group showed similar acute renal failure and mortality rate to the ischaemic non-treated group, serum creatinine decreased to levels similar to UNx group, which were maintained until the end of the study. Treatment of ischaemic kidneys with UR-12670 produced a slight decrease in 24-h proteinuria and a reduction in glomerulosclerosis, the mean tubulointerstitial score and number of monocyte-macrophages to values similar to UNx group.

CONCLUSIONS:

The chronic administration of the PAF antagonist UR-12670 attenuates the long-term effects of ischaemia-reperfusion injury in uninephrectomized ageing rats. The beneficial effect of this agent suggests that PAF contributes to the progression to late renal damage in this model.

• Authors: N Lloberas, J M Cruzado, J Torras, I Herrero-Fresneda, M Riera, M Merlos, J M Grinyó
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 16 Issue 4 Pg. 735-41 (Apr 2001) ISSN: 0931-0509 [Print] England
• PMID: 11274266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Imidazoles
• Platelet Aggregation Inhibitors
• Pyridines
• UR 12670

Topics

• Administration, Oral
• Aging
• Animals
• Chronic Disease
• Imidazoles (administration & dosage, therapeutic use)
• Ischemia (drug therapy, physiopathology)
• Kidney (blood supply, physiopathology)
• Kidney Diseases (drug therapy, physiopathology)
• Nephrectomy
• Platelet Aggregation Inhibitors (administration & dosage, therapeutic use)
• Pyridines (administration & dosage, therapeutic use)
• Rats
• Temperature