Selective Cox-2 Inhibition Markedly Slows Disease Progression and Attenuates Altered Prostanoid Production in Han:sprd-cy Rats with Inherited Kidney Disease.
From: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
American journal of physiology. Renal physiology
- Publish Date: Sep 2007
- ISSN: 0363-6127
- Volume: 293
- Issue: 3
- Pages: F821-30
- Medium: Print
- Language: English
- Citation (JAMA): Sankaran Deepa, Bankovic-Calic Neda, Ogborn Malcolm R, et al. Selective Cox-2 Inhibition Markedly Slows Disease Progression and Attenuates Altered Prostanoid Production in Han:sprd-cy Rats with Inherited Kidney Disease.. Am. J. Physiol. Renal Physiol. Sep 2007;293:F821-30
Abstract
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.
Mesh Headings (Keywords): Animals, Cyclooxygenase Inhibitors, Kidney, Kidney Diseases, Nitrobenzenes, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Rats, Rats, Inbred Strains, Sulfonamides
Check for Full Text / PubMed Unique Identifier (PMID): 17537981
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