PMID- 16407880
OWN - NLM
STAT- MEDLINE
DCOM- 20060726
LR  - 20071115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 69
IP  - 3
DP  - 2006 Feb
TI  - Pivotal role of xanthine oxidase in the initiation of tubulointerstitial renal 
      injury in rats with hyperlipidemia.
PG  - 481-7
AB  - Hyperlipidemia can induce or aggravate renal tubulointerstitial injury. 
      Experiments in a complex rat model with chronic glomerulonephritis and 
      long-standing, coexisting hyperlipidemia suggested that induction of xanthine 
      oxidase (XO), with increased oxygen radical generation, is involved in 
      aggravation of tubulointerstitial injury. To separate the role of XO in the 
      initial events of lipid-mediated tubulointerstitial injury, short-term 
      experiments with diet-induced hyperlipidemia over 21 and 35 days were performed 
      in otherwise healthy rats. XO expression in relation to the antioxidant enzymes 
      was examined in the cortical tubulointerstitium (TIS) and proximal tubules (PT). 
      Subsequent experiments with XO inhibition were performed, examining 
      tubulointerstitial infiltration with ED1-positive cells and expression of 
      adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) as indicators 
      of early injurious events. Hyperlipidemia increased XO activity in TIS by 40 and 
      86%, and in PT by 28 and 90% at days 21 and 35, compared with controls on regular 
      diet. This increased activity was associated with increased reactive oxygen 
      species. Among the antioxidant enzymes, glutathione peroxidase activity increased 
      in TIS by 40% and in PT by 90%. Histological evaluation showed a three-fold 
      increase in ED1-positive cells and increased MCP-1 and vascular cell adhesion 
      molecule-1 (VCAM-1) expression at day 35 in the TIS. Inhibition of XO prevented 
      tubulointerstitial ED1 cell infiltration, together with a decreased expression of 
      MCP-1 and VCAM-1. These results point to an important role for XO in the early 
      stage of hyperlipidemia-associated renal injury, mediating macrophage 
      infiltration by a putatively redox-dependent upregulation of MCP-1 and VCAM-1.
FAU - Gwinner, W
AU  - Gwinner W
AD  - Department of Nephrology, Medical School of Hannover, Hannover, Germany. 
      gwinner.wilfried@mh-hannover.de
FAU - Scheuer, H
AU  - Scheuer H
FAU - Haller, H
AU  - Haller H
FAU - Brandes, R P
AU  - Brandes RP
FAU - Groene, H-J
AU  - Groene HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Antioxidants)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Ectodysplasins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factors)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
SB  - IM
MH  - Animals
MH  - Antioxidants/therapeutic use
MH  - Cell Adhesion Molecules/analysis/genetics/physiology
MH  - Chemokine CCL2/analysis/genetics/physiology
MH  - Ectodysplasins
MH  - Glomerulonephritis/metabolism/pathology/physiopathology
MH  - Hyperlipidemias/drug therapy/*physiopathology
MH  - Immunohistochemistry
MH  - Kidney Tubules/chemistry/pathology/physiopathology
MH  - Macrophages/chemistry/pathology/physiology
MH  - Male
MH  - Membrane Proteins/analysis
MH  - Nephritis, Interstitial/*enzymology/pathology/*physiopathology
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Necrosis Factors/analysis
MH  - Up-Regulation
MH  - Vascular Cell Adhesion Molecule-1/analysis/genetics/physiology
MH  - Xanthine Oxidase/analysis/genetics/*physiology
EDAT- 2006/01/13 09:00
MHDA- 2006/07/27 09:00
CRDT- 2006/01/13 09:00
PHST- 2006/01/13 09:00 [pubmed]
PHST- 2006/07/27 09:00 [medline]
PHST- 2006/01/13 09:00 [entrez]
AID - S0085-2538(15)51513-5 [pii]
AID - 10.1038/sj.ki.5000121 [doi]
PST - ppublish
SO  - Kidney Int. 2006 Feb;69(3):481-7. doi: 10.1038/sj.ki.5000121.