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ToxSci Advance Access published online on June 12, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm132
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Modifications of Inflammatory Pathways in Rat Intestine Following Chronic Ingestion of Depleted Uranium

I Dublineau*, L Grandcolas, S Grison, C Baudelin, F Paquet, P Voisin, J Aigueperse and P Gourmelon

IRSN, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie expérimentale, IRSN, BP 17, F-92262 FONTENAY-aux-ROSES CEDEX, France

* Corresponding author (email: isabelle.dublineau{at}irsn.fr)

Received March 9, 2007; revision received March 29, 2007; accepted April 26, 2007


  Abstract

The environmental contamination by dispersion of depleted uranium (DU) might result in its chronic ingestion of DU by local populations. The aim of this study was to determine if chronic ingestion of DU at low doses induces inflammatory reactions in intestine, first biological system exposed to uranium after ingestion. Experiments were performed with 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 after 6 months, with no changes in PGE2 levels. At the same time, a decrease in mast cell number was observed without any changes in histamine levels. Experiments on cytokines showed increased gene expression of IL-1ß and IL-10 at 6 months, and decreased mRNA level of CCL-2. This change was associated with decreased macrophage density. An opposite effect of DU was induced on neutrophils, since decreased number was observed at 3 (x1.7) and 9 months (x3). The results obtained on NO pathway seemed to indicate that DU exposure inhibited this pathway (decreased eNOS mRNA, iNOS activity and NO2–/NO3–levels) at 6 months.

In conclusion, this study demonstrated that chronic ingestion of DU induced time-dependent modifications of inflammatory pathways, notably in terms of immune cell content. The ultimate effects of DU contamination might be pathogenic by suppressing defense mechanisms or inducing hypersensitivity. Further experiments should be thus performed to determine real consequences on intestinal response to oral antigens.

Key Words: uranyl nitrate; prostaglandins; cytokines; nitric oxide; immune cells.


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[Abstract] [Full Text] [PDF]


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