INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
capítulos de libros
Actualization in the understanding of the role of iron in inflammation and sepsis
GALLEANO MONICA; PUNTARULO SUSANA
Free Radical Pathophysiology.
Transworld Research Network
Lugar: Kerala-India; Año: 2008; p. 255 - 270
Iron (Fe) role in oxidative stress in mammals has been extensively studied, however, an important part of that acquired knowledge seems to require further revision after the multiple functions of nitric oxide (NO) started to be understood. This work summarizes the Fe metabolism, including the new discovered proteins, analyzing the Fe distribution into the intracellular and extracellular compartments. Inflammation and sepsis share a set of mechanisms triggered by the release of a group of cytokines, and one of the best known effects is the hypoferremia. The decrease in Fe availability in circulation would be responsible of limiting microorganisms growth and maintaining oxidative stress processes in a moderate extension. To explore the interaction between Fe and NO in vivo, rats were either injected with saline solution i.p. (control group) or with 200 mg of Fe/kg as Fe-dextran i.p. (Fe overloaded group). After 24 h, the animals were injected i.p. with 4 mg/kg of LPS and euthanized at 0 h, 3 h and 6 h post-LPS administration. Control rats showed a markedly decrease in Fe content in plasma (66%) during the initial 6 h period post-LPS administration while Fe-overloaded rats showed only a slight decrease (14%). Thus, even when sequestering mechanisms are operative, an Fe excess in circulation cannot be controlled by the mechanisms triggered by LPS, as it appears to occur in control animals. Oxidative stress in plasma was monitored by the ascorbyl radical content (A)/ascorbate content (AH-) (A/AH-) ratio. Fe-overloaded rats showed a significant increase in the ratio A/AH-. However, this parameter was not affected by LPS administration suggesting that the Fe-mediated oxidative processes when Fe levels are higher than under physiological conditions, would not be modulated by the substance/s released during the early period of endotoxemia.