Gamma-Irradiation Effect on Iron Metabolism in Brain Precursor cells. Role of Nitric Oxide.

ROBELLO E; GALATRO A; DUBNER D; PUNTARULO S

Montevideo, Uruguay

Congreso; Free Radicals in Montevideo 2007. V Meetin of SFRBM- South American Group. V International Conference on Peroxynitrite and Reactive Nitrogen Species; 2007

The effect of  irradiation on both Fe and ferritin (Ft) content in the developing rat brain irradiated in utero was studied. Pregnant Wistar rats were irradiated with 1 Gy at 17th day of the gestational period, and samples of maternal blood and fetal brains were taken at 1, 2 or 4 h post-irradiation. Labile Fe pool (LIP) in maternal plasma was assessed employing calcein. A significant increase in the LIP was observed after 4 h (1.90.3, 3.70.7, 41 and 51 M, for non-irradiated, and irradiated plasma after 1, 2 and 4 h, respectively). Total Fe content was determined assessing the formation of Fe2+-batophenanthroline complex. Total Fe content was 605, 1406, 11415 and 14412 pmol/mg tissue for non-irradiated brains, and for irradiated brains after 1, 2 and 4 h, respectively, showing a significant increase since 1 h post irradiation. LIP in the brains was significantly decreased at 2 h post irradiation (1.00.2 pmol/mg tissue) as compared to control values (3.80.6 pmol/mg tissue), without significant changes at 1 and 4 h (4.90.6 and 3±1 pmol/mg tissue, respectively). Ft content in the brain was assessed by Western blotting. Ft content decreased to 2314% of the control value after 2 h. Since previous data (Neurotoxicology, 2003, 24: 245-253) indicated that nitric oxide (NO), control rat brains were exposed in vitro to NO (100 nM) by treatment with 10 M S-nitrosoglutathione (GSNO) during 2, 15 and 30 min, and LIP was assessed in the homogenate afterwards. The LIP was decreased by 84, 89 and 96%, respectively after 2, 15 and 30 min of the exposure, as compared to non-treated brains. These results suggest that irradiation of the developing rat brain triggered a network of signals that affected NO concentration, and due to the NO ability to chelate Fe, Fe metabolism was affected. Supported by grants from CONICET, UBA and ANPCyT.