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

American Journal of Physiology - Renal Physiology - Tập 293 Số 3 - Trang F821-F830 - 2007
Deepa Sankaran1, Neda Bankovic‐Calic, Malcolm R. Ogborn, G. H. Crow, Harold M. Aukema
1Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2

Tóm tắt

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 B2and PGE2levels, 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.

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