Modifications of Inflammatory pathways in rat intestine following chronic ingestion of depleted uranium
Journal title : Toxicological Sciences
Volume : 98
Issue : 2
Pagination : 458-468
Publication date : 01/08/2007
The use of depleted uranium (DU) led to dispersion of this radionuclide in the environment resulting in the contamination of water wells and food chain. The aim of this study was to determine if chronic ingestion of DU at low doses may induce inflammatory reactions in intestine, first biological system exposed to uranium after ingestion. Experiments were performed in rats receiving uranium in drinking water (40mg/L) during 3, 6 or 9 months. Several parameters referring to prostaglandin, histamine, cytokine and nitric oxide pathways were assessed in ileum. Concerning the prostaglandin pathway, a 2-fold increase in gene expression of Cox2 was noted at 6 months, with no changes in PGE2 levels. No changes in histamine levels were observed after uranium exposure, despite a decrease in mast cell number at 6 months. The results obtained on the NO pathway indicated that gene expression and enzyme activity of constitutive NOS was increased (x2.5) by DU exposure with slight decrease in inducible NOS. Measurements of cytokine pathway showed slight increase in gene expression of pro- and anti-inflammatory mediators at 6 months, associated with decrease in mRNA level of CCL-2. This change was associated with modification on density of macrophages in intestine. Finally, an increase of neutrophil number was observed at 3 (x170%) and 9 months (x300%).
In conclusion, this study demonstrated that chronic ingestion of depleted uranium induced time-dependent modifications of inflammatory pathways in rat intestine. Further experiments should be performed to determine the consequences of these modifications on the functionality of mucosal immunity.