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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/F821    most recent 00257.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Sankaran, D. Articles by Aukema, H. M. Search for Related Content PubMed PubMed Citation Articles by Sankaran, D. Articles by Aukema, H. M.

Selective COX-2 inhibition markedly slows disease progression and attenuates altered prostanoid production in Han:SPRD-cy rats with inherited kidney disease

Departments of ¹Human Nutritional Sciences, ²Pediatrics and Child Health, and ³Animal Sciences, University of Manitoba, and ⁴Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada

Submitted 6 July 2006 ; accepted in final form 25 May 2007

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.

NS-398; histology; cyclooxygenase activity