Iron attenuates nitric oxide level and iNOS expression in endotoxin-treated mice.
The effect of exogenous Fe-citrate complex (Fe doses of 120 and 240 micromol/kg) on nitric oxide (NO) production in vivo has been studied in blood and liver tissue of endotoxin-treated mice. Fe-citrate complex was administered to mice subcutaneously at the same time with intravenous injection of Escherichia coli lipopolysaccharide (LPS). Iron-dependent decrease in NO2-/NO3- and nitrosyl hemoglobin levels in blood of animals was detected at 6 h after LPS administration, suggesting systemic attenuation of NO generation. NO production in the liver tissue of LPS-treated mice was decreased after Fe administration judging from the amount of mononitrosyl-iron complexes formed in the tissue by diethyldithiocarbamate. The iNOS protein determination in the liver tissue of LPS-treated mice demonstrated iron-dependent inhibition of iNOS expression. We have found previously that exogenous iron does not affect systemic NO level when it is given at 6 h after LPS injection, i.e. after iNOS expression. This is a first report demonstrating iron-dependent iNOS down-regulation in endotoxin-treated mice.
Komarov
A M
AM
Division of Experimental Medicine, The George Washington University Medical Center, Washington, DC 20037, USA. amkoma@gwis2.circ.gwu.edu
Mattson
D L
DL
Mak
I T
IT
Weglicki
W B
WB
D000818:Animals; D019343:Citric Acid / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*
D004731:Endotoxins; D019343:Citric Acid; D009569:Nitric Oxide; D004050:Ditiocarb; D007501:Iron; D019001:Nitric Oxide Synthase