title: Marginal zinc deficiency exacerbates experimental colitis induced by dextran sulfate sodium in rats.
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 TNFα 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 30 μmol/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 and TNFR1 expression rather than through the impairment of epithelial barrier function.
authors.affiliation: Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589 Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iwaya
authors.forename: Munenori
authors.initials: M
authors.lastname: Kashiwaya
authors.forename: Aki
authors.initials: A
authors.lastname: Shinoki
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishizuka
mesh_terms: D000818:Animals; D003092:Colitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D015870:Gene Expression; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D015032:Zinc / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*
chemical_list: D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506237:Tnfrsf1a protein, rat; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D009195:Peroxidase; D015032:Zinc