Selective COX-2 inhibition markedly slows disease progression and attenuates altered prostanoid production in Han:SPRD-cy rats with inherited kidney disease.
Selective cyclooxygenase-2 (COX-2) inhibitors appear to have beneficial renoprotective effects in most, but not all, renal disease conditions. The objective of our study was to examine the effects of COX-2 inhibition in a rat model of polycystic kidney disease. Four-week-old Han:SPRD-cy rats were given a standard rodent diet containing NS-398 (3 mg.kg body wt(-1).day(-1)) or a control diet without NS-398 for 7 wk. In diseased rats, selective COX-2 inhibition resulted in 18% and 67% reduction in cystic expansion and interstitial fibrosis, respectively, but no change in renal function. NS-398 also ameliorated disease-associated pathologies, such as renal inflammation, cell proliferation, and oxidant injury (by 33, 38, and 59%, respectively). Kidney disease was associated with elevated renal COX-1 and COX-2 enzyme activities, and NS-398 blunted the increase in COX-2 enzyme activity (as indicated by 21 and 28% lower renal thromboxane B2 and PGE2 levels, respectively). NS-398 reduced urinary excretion of prostanoid metabolites in diseased rats. In summary, COX-2 inhibition attenuated renal injury, reduced the elevated renal COX-2 activity, and ameliorated disease-related alterations in prostanoid production in this rat model of chronic renal disease.
Sankaran
Deepa
D
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
Bankovic-Calic
Neda
N
Ogborn
Malcolm R
MR
Crow
Gary
G
Aukema
Harold M
HM
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D009578:Nitrobenzenes / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D011451:Prostaglandin-Endoperoxide Synthases