title: Oral exposure to cadmium chloride triggers an acute inflammatory response in the intestines of mice, initiated by the over-expression of tissue macrophage inflammatory protein-2 mRNA.
abstract: Intestinal inflammation is an indispensable protective response of the gut immune system to aggressive injury from pathogens and/or chemicals. Although the major route of exposure to cadmium for most people is via food, causing the gastrointestinal tract to become the first target organ, very little information is available on whether cadmium exposure triggers the intestinal inflammatory response. We investigated in the present study the acute inflammatory response in the intestines of mice orally challenged with a single dose of cadmium chloride (CdCl(2)) by determining the gene expression of pro-inflammatory mediators with real-time PCR, and by examining the infiltration of inflammatory cells with a myeloperoxidase (MPO) assay and histological analysis of hematoxylin and eosin (H&E)-stained intestinal sections. The results show that CdCl(2) significantly increased the expression of macrophage inflammatory protein-2 mRNA (30-40 times the normal level) 3h and the activity of MPO (about 2 times the normal level) 24h after the challenge in the duodenal and proximal jejunal tissue. Furthermore, these increases were dose-dependent over a dosage range of 25-100mg/kg of body weight. The histological analysis confirmed that CdCl(2) induced mild to moderate villus damage and infiltration of inflammatory cells into the lamina propria. All these results demonstrate that oral exposure to CdCl(2) triggered an acute inflammatory response in the proximal intestine of mice, suggesting that the gut immune system was involved in the toxic effects of Cd on the gastrointestinal tract.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. zhaohuizhao@hotmail.com
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhao
authors.forename: Ja Shil
authors.initials: JS
authors.lastname: Hyun
authors.forename: Hideo
authors.initials: H
authors.lastname: Satsu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000187:drug effects*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009195:Peroxidase / Q000378:metabolism
chemical_list: D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D009195:Peroxidase; D019256:Cadmium Chloride