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Chronic ingestion of depleted uranium modified inflammatory pathways in rat intestine


Congress title :International Congress of Toxicology
Congress town :Montréal
Congress date :15/07/2007

Summary

The potential hazard of chronic exposure to depleted uranium (DU) due to its environmental dispersion is of increasing concern. The aim of this work was to determine effects of chronic ingestion of DU at low doses on inflammatory pathways (prostaglandins, histamine, cytokines and NO) in small intestine. Experiments were performed in rats receiving DU in drinking water (40mg/L) during several months. Inflammatory mediators, synthesis enzymes (COX and NOS) and immune cells (mast cells, macrophages and neutrophils) were assessed by using semi-quantitative RT-PCR, ELISA kits, colorimetric methods and immunohistochemistry. At 6 months, a 2-fold increase in gene expression of Cox2 was noted, with no changes in PGE2 levels. At the same time, decrease in mast cell number was observed without any changes in histamine levels. Experiments showed also an increase in gene expression of IL-1b and IL-10, and a decrease in mRNA level of CCL-2. This change was associated with a decreased density of macrophages in intestine. An opposite effect of DU was induced on neutrophils with an increased content at 3 (x1.7) and 9 months (x3). In addition, results obtained at 6 months indicated that DU inhibited NO pathway (decreased eNOS mRNA, iNOS activity and NO2-/NO3- levels) as did lead. In conclusion, this study demonstrated that chronic DU ingestion affected immune cell content in small intestine. The consequences of such modifications on intestinal response to oral antigens remained to be determined.

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