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 mu mol/kg) on nitric oxide (NO) production in vivo has been studied in b lood and liver tissue of endotoxin-treated mice, Fe-citrate complex wa s administered to mice subcutaneously at the same time with intravenou s injection of Escherichia coli lipopolysaccharide (LPS), Iron-depende nt decrease in NO2-/NO3- and nitrosyl hemoglobin levels in blood of an imals was detected at 6 h after LPS administration, suggesting systemi c attenuation of NO generation, NO production in the liver tissue of L PS-treated mice was decreased after Fe administration judging from the amount of mononitrosyl-iron complexes formed in the tissue by diethyl dithiocarbamate. The iNOS protein determination in the liver tissue of LPS-treated mice demonstrated iron-dependent inhibition of iNOS expre ssion, We have found previously that exogenous iron does not affect sy stemic NO level when it is given at 6 h after LPS injection, i.e. afte r iNOS expression, This is a first report demonstrating iron-dependent iNOS down-regulation in endotoxin-treated mice, (C) 1998 Federation o f European Biochemical Societies.