PMID- 21378157
OWN - NLM
STAT- MEDLINE
DCOM- 20110930
LR  - 20220318
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 26
IP  - 6
DP  - 2011 Jun
TI  - 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.
PG  - 1785-96
LID - 10.1093/ndt/gfr035 [doi]
AB  - 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. 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. 
      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. 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.
FAU - Zuo, Jian
AU  - Zuo J
AD  - Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, 
      University of Florida, Gainesville, FL, USA.
FAU - Khan, Aslam
AU  - Khan A
FAU - Glenton, Patricia A
AU  - Glenton PA
FAU - Khan, Saeed R
AU  - Khan SR
LA  - eng
GR  - R01 DK078602/DK/NIDDK NIH HHS/United States
GR  - R01-DK078602/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110304
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Havcr1protein, rat)
RN  - 0 (Oxalates)
RN  - 0 (Reactive Oxygen Species)
RN  - 106441-73-0 (Osteopontin)
RN  - 2612HC57YE (Calcium Oxalate)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - RMB44WO89X (Hydroxyproline)
SB  - IM
CIN - Nephrol Dial Transplant. 2011 Jun;26(6):1759-61. PMID: 21551084
MH  - Animals
MH  - Blotting, Western
MH  - Calcium Oxalate/*metabolism
MH  - Cell Adhesion Molecules/*metabolism
MH  - Chemokine CCL2/metabolism
MH  - Hydroxyproline/*toxicity
MH  - Hyperoxaluria/*chemically induced/*metabolism
MH  - Immunoenzyme Techniques
MH  - Kidney/cytology/drug effects/*metabolism
MH  - Male
MH  - NADPH Oxidases/*antagonists & inhibitors/metabolism
MH  - Osteopontin/metabolism
MH  - Oxalates/pharmacology
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
PMC - PMC3145402
EDAT- 2011/03/08 06:00
MHDA- 2011/10/01 06:00
PMCR- 2012/06/01
CRDT- 2011/03/08 06:00
PHST- 2011/03/08 06:00 [entrez]
PHST- 2011/03/08 06:00 [pubmed]
PHST- 2011/10/01 06:00 [medline]
PHST- 2012/06/01 00:00 [pmc-release]
AID - gfr035 [pii]
AID - 10.1093/ndt/gfr035 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2011 Jun;26(6):1785-96. doi: 10.1093/ndt/gfr035. Epub 
      2011 Mar 4.