PMID- 16164630
OWN - NLM
STAT- MEDLINE
DCOM- 20051230
LR  - 20181201
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 68
IP  - 4
DP  - 2005 Oct
TI  - Parenteral iron treatment induces MCP-1 accumulation in plasma, normal kidneys, 
      and in experimental nephropathy.
PG  - 1533-42
AB  - INTRODUCTION: Monocyte chemoattractant protein-1 (MCP-1) promotes renal 
      inflammation, thereby contributing to acute and chronic nephropathies. Its 
      production is stimulated by oxidative stress. Thus, this study tested whether 
      pro-oxidant iron/carbohydrate complexes, used to treat iron deficiency, induce 
      MCP-1 in renal/extrarenal tissues, in plasma, and in the setting of experimental 
      nephropathy. METHODS: CD-1 mice received 2 mg of intravenous iron [complexed with 
      dextran (iron dextran), sucrose (iron sucrose), or gluconate (iron gluconate)]. 
      Renal MCP-1 and/or its mRNA were measured 3 hours to 7 days post-iron injection. 
      Iron effects on liver, lung, spleen, and heart MCP-1 mRNA, and on peritoneal 
      lavage fluid MCP-1 concentrations were assessed. Iron pretreatment effects on 
      MCP-1 levels in unilaterally obstructed kidneys vs. contralateral kidneys were 
      determined. Finally, iron gluconate's influence on proximal tubule [human 
      kidney-2 (HK-2)] cell MCP-1 levels was assessed. RESULTS: Iron sucrose (the 
      primary test agent) markedly increased plasma and renal MCP-1 levels. It also 
      induced multiorgan MCP-1 mRNA increments (liver > spleen > kidney > lung > 
      heart). Iron gluconate was more potent than iron sucrose; conversely, iron 
      dextran had no discernible effect. The iron dextran and iron sucrose-induced 
      renal MCP-1 mRNA increments ( approximately 4x) were persistent, lasting for at 
      least 3 to 7 days. Iron gluconate raised MCP-1 levels in peritoneal lavage fluid. 
      It also doubled MCP-1 in unilaterally obstructed kidneys (ureteral ligation) 
      without altering contralateral (control kidney) MCP-1 content. Iron gluconate 
      raised HK-2 cell MCP-1, implying a direct proximal tubule effect. CONCLUSION: 
      Iron sucrose and iron gluconate (but not iron dextran) can induce MCP-1 
      generation in renal and extrarenal tissues, possibly via transcriptional events. 
      This may dramatically impact renal disease-induced MCP-1 increments. Finally, 
      iron can increase peritoneal lavage fluid MCP-1 levels. Whether the above changes 
      have implications for renal disease progression, and/or for peritoneal 
      inflammation/peritoneal dialysis efficiency, are issues which may need to be 
      addressed.
FAU - Zager, Richard A
AU  - Zager RA
AD  - Department of Medicine, University of Washington, Seattle, Washington 98109, USA. 
      dzager@fhcrc.org
LA  - eng
GR  - R01 DK68520-01/DK/NIDDK NIH HHS/United States
GR  - R37 DK38432-18/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Ferric Compounds)
RN  - 0 (Gluconates)
RN  - 0 (RNA, Messenger)
RN  - 9004-66-4 (Iron-Dextran Complex)
RN  - FZ7NYF5N8L (Ferric Oxide, Saccharated)
RN  - QLZ991V4A2 (Glucaric Acid)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*blood/*genetics
MH  - Ferric Compounds/pharmacology
MH  - Ferric Oxide, Saccharated
MH  - Gene Expression/drug effects
MH  - Glucaric Acid
MH  - Gluconates/pharmacology
MH  - Humans
MH  - Injections, Intravenous
MH  - Iron-Dextran Complex/*pharmacology
MH  - Kidney Cortex/cytology/*physiology
MH  - Kidney Diseases/blood/*physiopathology
MH  - Liver/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Oxidative Stress/drug effects
MH  - Peritoneum/physiology
MH  - RNA, Messenger/analysis
EDAT- 2005/09/17 09:00
MHDA- 2005/12/31 09:00
CRDT- 2005/09/17 09:00
PHST- 2005/09/17 09:00 [pubmed]
PHST- 2005/12/31 09:00 [medline]
PHST- 2005/09/17 09:00 [entrez]
AID - S0085-2538(15)51006-5 [pii]
AID - 10.1111/j.1523-1755.2005.00565.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Oct;68(4):1533-42. doi: 10.1111/j.1523-1755.2005.00565.x.