2048 EFFECT OF APOCYNIN ON EXPRESSION OF KIDNEY INJURY MOLECULE-1 & CAOX CRYSTAL DEPOSITION IN HYPEROXALURIC RATS

Abstract

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20112048 EFFECT OF APOCYNIN ON EXPRESSION OF KIDNEY INJURY MOLECULE-1 & CAOX CRYSTAL DEPOSITION IN HYPEROXALURIC RATS Saeed Khan, Aslam Khan, Patricia Glenton, and Jian Zuo Saeed KhanSaeed Khan Gainesville, FL More articles by this author , Aslam KhanAslam Khan Gainesville, FL More articles by this author , Patricia GlentonPatricia Glenton Gainesville, FL More articles by this author , and Jian ZuoJian Zuo Gainesville, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2279AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES High oxalate (Ox) and calcium oxalate (CaOx) crystals are injurious to cells and CaOx crystal deposition in kidneys is associated with renal injury and movement of inflammatory cells into the interstitium. We have proposed that Ox and CaOx crystal induced injury is most likely caused by reactive oxygen species (ROS) produced by activation of membrane associated NADPH oxidase. We determined the effect of NADPH oxidase inhibitor apocynin on renal CaOx crystal deposition and the expression of kidney injury molecule-1 (KIM-1), osteopontin (OPN), monocyte chemoattracatant protein-1 (MCP-1), and ED-1. METHODS Male Sprague-Dawley rats were fed a diet containing 5% HLP and 4mml apocynin to drink for 28 days. Urinary crystals, Ox , Ca, hydrogen peroxide (H2O2), NAG, KIM-1, OPN, and MCP-1 were determined. Paraffin embedded kidneys were stained using H&E, PAS. Calcium oxalate crystals were identified by Pizzzolato staining as well as use of polarizing optics. Kidney sections were processed for immunohistochemistry using specific antibodies against KIM-1, OPN and ED1. Semi-quantitative evaluation of protein in kidneys was performed with computer-assisted densitometric scanning of western blots. RESULTS Hyperoxaluria produced heavy deposits of CaOx crystals. Renal tubules with the crystals appeared dilated. There was a significant increase in urinary excretion of KIM-1, OPN, H2O2 and MCP-1 and renal expression of KIM-1 and OPN. Staining was seen associated with the crystal deposits as well as in epithelial cells not in apparent contact with the cells. ED-1 positive cells, which were totally absent in the control kidneys, were present in the renal interstitium of hyperoxaluric rats. Apocynin treatment resulted in 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 H2O2. Apocynin had no effect on the urinary excretion of Ox or NAG. CONCLUSIONS Data presented here demonstrate that inhibition of NADPH oxidase by apocynin resulted in the reduction of crystal deposition without significant effect upon urinary Ox. Crystal deposition was associated with increased renal expression of KIM-1, OPN, MCP-1, ED-1, markers of injury and inflammation which were also reduced by apocynin treatment. Results provide support to our proposal that renal epithelial injury is critical for crystal retention within the renal tubules and that injury is in part caused by the production of ROS with the involvement of NADPH oxidase. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e820 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Saeed Khan Gainesville, FL More articles by this author Aslam Khan Gainesville, FL More articles by this author Patricia Glenton Gainesville, FL More articles by this author Jian Zuo Gainesville, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...