Parenteral iron treatment induces MCP-1 accumulation in plasma, normal kidneys, and in experimental nephropathy

Kidney Int. 2005 Oct;68(4):1533-42. doi: 10.1111/j.1523-1755.2005.00565.x.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Cells, Cultured
  • Chemokine CCL2 / blood*
  • Chemokine CCL2 / genetics*
  • Ferric Compounds / pharmacology
  • Ferric Oxide, Saccharated
  • Gene Expression / drug effects
  • Glucaric Acid
  • Gluconates / pharmacology
  • Humans
  • Injections, Intravenous
  • Iron-Dextran Complex / pharmacology*
  • Kidney Cortex / cytology
  • Kidney Cortex / physiology*
  • Kidney Diseases / blood
  • Kidney Diseases / physiopathology*
  • Liver / physiology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Oxidative Stress / drug effects
  • Peritoneum / physiology
  • RNA, Messenger / analysis

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Ferric Compounds
  • Gluconates
  • RNA, Messenger
  • Iron-Dextran Complex
  • Ferric Oxide, Saccharated
  • Glucaric Acid