Effect of endotoxemia generated by LPS administration on Fe content in rat brain

PILONI N.E., ROBELLO E. AND PUNTARULO S.

Los Cocos, Provincia de Córdoba

Congreso; Biofísica de Sistemas Autoorganizados; 2009

Among the multiple functions of NO, it started to be understood that NO-Fe interactions are important features of the inflammation process. The decrease in Fe availability in circulation in endotoxemia would be responsible for limiting micro-organisms growth, and maintaining oxidative stress processes in a moderate extension. To explore the interaction between Fe and NO in rat brain in vivo, rats were either injected with saline solution i.p. (control group), with 200 mg of Fe/kg as Fe-dextran i.p. (Fe-overloaded group), with 4 mg/kg of LPS i.p. (LPS group), or with 200 mg of Fe/kg as Fe-dextran together with 4 mg/kg of LPS i.p. (Fe-LPS group), and euthanized at  6 h post-administration. Total Fe content was analyzed employing bathophenanthroline by monitoring the absorbance at l=535 nm. Total Fe content showed no difference between control and LPS groups (52±6 and 78±25 mg/g DW, respectively), meanwhile in Fe-overloaded group total Fe content significantly increased (8.3-fold) as compared to control values. The simultaneous administration of LPS and Fe (Fe-LPS group) increased Fe content by 19-fold. The labile Fe pool (LIP) in brain homogentes was studied by a fluorescence technique employing calcein (CA). The LIP content was 21±3 pmol Fe/mg FW in control group, and was not significantly affected by LPS administration. The LIP in Fe overloaded rats after administration of LPS (Fe-LPS group) synergistically increased (90±17 pmol Fe/mg FW) as compared to LIP in Fe overloaded group (50±5 pmol Fe/mg FW). The data presented here showed that the decrease in Fe content in plasma by endotoxemia is accompanied by an increase in the total Fe content in the brain. Moreover, the increased observed in the LIP when Fe excess was accompanied by LPS administration, could enhance the potentially damaging effects by oxidative pathways. Thus, even when Fe sequestering mechanisms are operative in plasma, Fe excess during endotoxemia could lead to severe damaging effects in brain.