Nitric oxide and iron: effect of iron overload on nitric oxide production in endotoxemia

GALLEANO M.; SIMONTACCHI M; PUNTARULO S

MOLECULAR ASPECTS OF MEDICINE

Elsevier Science

Lugar: Londres; Año: 2004 vol. 25 p. 141 - 154

0098-2997

  The amount of iron within the cell is carefully regulated in order to provide an adequate level of micronutrient while preventing its accumulation and toxicity. Iron excess is believed to generate oxidative stress, understood as an increase in the steady state concentration of oxygen radical intermediates. Nitric oxide (NO) is an inorganic free-radical gaseous molecule which has been shown over the last decade to play an unprecedented variety of roles in biological systems. The effect of nitrogen reactive species may explain the iron sequestration pattern that characterizes macrophages under inflammatory conditions. From a patho-physiologic viewpoint, further studies are required to assess the usefulness of this mechanism to minimize formation and release of free radicals in diseased tissues. However, contrary to the deleterious effects of the reactive nitrogen oxide species formed from either NO/O2 and NO/O2-, it has been pointed out that NO shows antioxidant properties. A number of studies have described the complex relationships between iron and NO, but controversy remains as to the influence and significance of iron on inflammatory NO production. To explore the initial steps of the effects triggered by LPS administration in the presence of excess iron, male Wistar rats were treated with saline solution; dextran ip; lipopolysaccharide from Escherichia coli (serotype 0127:B8) (LPS) ip; iron dextran ip; or iron dextran plus LPS. Samples were obtained 6 h after administration. EPR spectra of NO-Hb in the venous blood were detected at 77 K. Iron-dextran administered to rats intraperitoneally resulted predominantly in iron uptake by the liver Kupffer cells, and leading to an increased NO production in blood in the presence of LPS. Further studies will be required to assess the complex role of the Kupffer cells on iNOS induction and NO production.However, contrary to the deleterious effects of the reactive nitrogen oxide species formed from either NO/O2 and NO/O2-, it has been pointed out that NO shows antioxidant properties. A number of studies have described the complex relationships between iron and NO, but controversy remains as to the influence and significance of iron on inflammatory NO production. To explore the initial steps of the effects triggered by LPS administration in the presence of excess iron, male Wistar rats were treated with saline solution; dextran ip; lipopolysaccharide from Escherichia coli (serotype 0127:B8) (LPS) ip; iron dextran ip; or iron dextran plus LPS. Samples were obtained 6 h after administration. EPR spectra of NO-Hb in the venous blood were detected at 77 K. Iron-dextran administered to rats intraperitoneally resulted predominantly in iron uptake by the liver Kupffer cells, and leading to an increased NO production in blood in the presence of LPS. Further studies will be required to assess the complex role of the Kupffer cells on iNOS induction and NO production.