Effect of aspirin and sulindac in rabbit nephrotoxic nephritis.
Glomerular damage in nephrotoxic nephritis is mediated by circulating cells (neutrophils, platelets, and macrophages) infiltrating the glomerular tuft and responsible for the inflammatory reactions. It has been suggested that inflammatory cells may participate in glomerular inflammation through the synthesis and release of eicosanoids derived from the metabolism of arachidonic acid. On the other hand, old data and recent evidence indicate that eicosanoids derived from renal arachidonic acid metabolism play an important role in maintaining hemodynamics, especially in disease conditions. We wanted to evaluate the differential role of arachidonic acid metabolites derived from circulating or renal cells on the evolution of nephrotoxic nephritis. We used a nonselective cyclooxygenase inhibitor, aspirin, which blocks eicosanoid synthesis both in circulating cells and in renal tissue, as compared with a selective cyclooxygenase inhibitor, sulindac, which inhibits arachidonic acid metabolism in circulating cells, partially sparing renal cyclooxygenase. Aspirin, at a dosage that almost completely inhibits both circulating cell and renal arachidonate metabolites, worsens the morphologic expression of rabbit nephrotoxic nephritis and negatively influences the clinical course of the disease. Sulindac, at a dose that suppresses circulating platelet cyclooxygenase activity by 90%, but only partially affects renal prostaglandin synthesis, prevents extracapillary proliferation and reduces proteinuria without negative influence on glomerular hemodynamics.
Bertani
T
T
Benigni
A
A
Cutillo
F
F
Rocchi
G
G
Morelli
C
C
Carminati
C
C
Verroust
P
P
Remuzzi
G
G
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D001485:Basement Membrane / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors; D007192:Indenes / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D009393:Nephritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D013467:Sulindac / Q000494:pharmacology*; D013931:Thromboxanes / Q000378:metabolism
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D007192:Indenes; D011453:Prostaglandins; D013931:Thromboxanes; D013467:Sulindac; D016718:Arachidonic Acid; D001241:Aspirin