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Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-L-proline-induced hyperoxaluria in the male Sprague-Dawley rats.
- Source :
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Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2011 Jun; Vol. 26 (6), pp. 1785-96. Date of Electronic Publication: 2011 Mar 04. - Publication Year :
- 2011
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Abstract
- Background: Renal calcium oxalate (CaOx) crystal deposition is associated with epithelial injury and movement of inflammatory cells into the interstitium. We have proposed that oxalate (Ox)- and CaOx crystal-induced injury is most likely caused by reactive oxygen species (ROS) produced by activation of membrane nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.<br />Methods: Present study was undertaken to determine the effect of NADPH oxidase inhibitor apocynin on the expression of kidney injury molecule-1 (KIM-1) and renal CaOx crystal deposition in rats with hyperoxaluria. We also investigated the urinary excretion of KIM-1, osteopontin (OPN) and monocyte chemoattractant protein-1 (MCP-1) and renal expression of OPN and ED-1. Male Sprague-Dawley rats were fed a diet containing 5% hydroxyl-L-proline (HLP) and 4 mmol apocynin to drink for 28 days. Urine was collected on Days 7, 14, 21 and 28. After that, rats were sacrificed and their kidneys processed for various microscopic and molecular investigations.<br />Results: HLP consumption produced heavy deposits of CaOx crystals. Renal expression of KIM-1 and OPN and urinary excretion of KIM-1, OPN, H(2)O(2) and MCP-1 was significantly increased. ED-1-positive cells migrated into renal interstitium. Apocynin treatment caused significant reduction of crystal deposits, injured and dilated tubules; renal expression of KIM-1, OPN and ED-1 and urinary excretion of KIM-1, OPN, MCP-1 and H(2)O(2). Apocynin had no effect on the urinary excretion of Ox.<br />Conclusions: This is the first study of urinary excretion and renal expression of KIM-1 in association with renal CaOx crystal deposition, experimental or clinical. The results indicate that NADPH oxidase inhibition leads to reduction in KIM-1 expression and urinary excretion as well as renal CaOx crystal deposition. KIM-1 is an important marker of renal epithelial injury. The results provide further support to our proposal that renal epithelial injury is critical for crystal retention and that injury is in part caused by the production of ROS with the involvement of NADPH oxidase.
- Subjects :
- Animals
Blotting, Western
Chemokine CCL2 metabolism
Immunoenzyme Techniques
Kidney cytology
Kidney drug effects
Male
NADPH Oxidases metabolism
Osteopontin metabolism
Oxalates pharmacology
Oxidative Stress
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Calcium Oxalate metabolism
Cell Adhesion Molecules metabolism
Hydroxyproline toxicity
Hyperoxaluria chemically induced
Hyperoxaluria metabolism
Kidney metabolism
NADPH Oxidases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2385
- Volume :
- 26
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
- Publication Type :
- Academic Journal
- Accession number :
- 21378157
- Full Text :
- https://doi.org/10.1093/ndt/gfr035