Marginal Zinc Deficiency Exacerbates Experimental Colitis Induced by Dextran Sulfate Sodium in Rats1231,2,3

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Abstract

We investigated the impact of Zn status on the maintenance of mucosal homeostasis. Rats were fed diets containing different amounts of Zn (30, 10, 5, <1 mg Zn/kg diet) for 21 d. Serum Zn concentrations were lower in rats fed marginally Zn-deficient (MZD; 5 mg Zn/kg diet) and severely Zn-deficient (<1 mg/kg) diets but not in those fed the marginally Zn-adequate diet (10 mg/kg) or the Zn-adequate (ZA; 30 mg/kg) group (P< 0.05). However, organ weights, colonic epithelial cell proliferation, and crypt fission did not differ between the MZD and ZA groups. We then evaluated whether MZD modulated dextran sulfate sodium (DSS)-induced colonic inflammation by administering 2% DSS to the MZD and ZA groups for 7 d. Myeloperoxidase activity and TNFa production increased in response to DSS in the MZD group (P <0.03). Colonic permeability in the 2 groups did not differ after DSS administration. In a culture experiment using isolated mesenteric leukocytes, TNFα production was higher (P< 0.05) and TNF receptor type I (TNFR1) expression was detected in culture medium containing 20 and 30μmol/L of Zn compared with culture medium lacking Zn supplementation. These results suggest that MZD exacerbated colitis by modulating the immune response through the impairment of TNFα production andTNFR1expression rather than through the impairment of epithelial barrier function.

Abbreviations used:

DAI
disease activity index
DSS,
dextran sulfate sodium
IBD
inflammatory bowel disease
LY
lucifer yellow
ML,
mesenteric leukocyte
MZA
marginally zinc adequate
MZD
marginally zinc deficient
PF
pair fed
PMN
polymorphonuclear neutrophil
ZA
zinc adequate
ZD
zinc deficient

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1

Supported by the Salt Science Research Foundation, no.0914.

2

Author disclosures: H. Iwaya, M. Kashiwaya, A. Shinoki, J. S. Lee, K. Hayashi,H. Hara, and S. Ishizuka, no conflicts of interest.

3

Supplemental Figures 1 and 2 and Supplemental Tables 1 and 2 are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at jn.nutrition.org.