Infectious agents that alter organ function may impact the toxicity of environmental chemicals. These perturbations could increase an individual's susceptibility to chemical exposures. Therefore, understanding the biochemical associations between infectious agents and environmental chemicals are of critical importance for safety assessment in human populations. In the current study, we investigated how mice infected with the enteric pathogen, Citrobacter rodentium, were impacted by arsenic exposure. C57BL/6J mice were pretreated with 100 ppb arsenic (NaAsO2) in the drinking water for four weeks and then gavaged with a single inoculum of C. rodentium. Pathology was assessed at Day 7 post-infection. Arsenic exposure enhanced C. rodentium pathology in the cecum and colon relative to non-arsenic-exposed C. rodentium-infected mice. These pathological features were hallmarked by enhanced inflammatory infiltrates and epithelial tattering. Arsenic-dependent changes in cytokines were observed among C. rodentium-infected animals. Notably, increased levels of granulocyte colony-stimulating factor (G-CSF) and CXCL1 (KC) were observed, which are indicative of neutrophil activation. These data suggest that even at modest levels of arsenic exposure, pathological outcomes are enhanced in individuals exposed to lower bowel inflammation.

Impact of infection and inflammation on arsenic toxicity

248th National Meeting (2014)

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