Zinc deficiency induces dysregulation of cytokine productions in an experimental colitis of rats

Abstract

Dextran sulfate sodium (DSS)-induced colitis is an experimental model of ulcerative colitis, although the precise mechanism has not yet been elucidated. We investigate whether Zn deficiency affects the pathogenesis of colitis induced by DSS with a focus on immune responses. Male WKAH/Hkm Slc rats were fed either a Zn-adequate (ZA, 30 mg Zn/kg diet) as a control or Zndeficient (ZD, 5 mg Zn/kg diet) diet for 21 days and then treated with 2% DSS via deionized drinking water for 7 days. The disease activity index (DAI) was recorded daily throughout DSS treatment. Serum Zn concentrations were significantly lowered in rats fed the ZD diet than those fed the ZA diet at day 7 and 14. Surprisingly, DSS treatment considerably reduced the serum Zn in both groups. The rats fed the ZD diet showed exacerbated colitis based on clinical outcomes, including weight loss, increased DAI, and shortened colon length. An in vitro study corroborated these results, showing that a large amount of TNFα was induced by rat mesenteric leukocytes in response to lipopolysaccharide in ZD medium, but not in ZA medium. These results indicate that a modulation of TNFα production due to Zn deficiency influences disease activity in DSS-induced colitis. In addition, more attention should be given to Zn for prevention of colitis.

Impact of dietary manganese on experimental colitis in mice

“…Previous studies using Se‐deficient diets (<0.01 mg/kg) showed that a time period of 12 weeks was required before Se deficiency resulted in any worsening in the colons of DSS‐induced colitis in mice . In contrast, rats fed a zinc‐deficient diet (5 mg/kg) for 3 weeks showed exacerbation of DSS‐induced colitis . In the present study, dietary Mn deficiency worsened the severity of experimental colitis and promoted IBD development in mice after feeding a low Mn diet for only 2 weeks, and the DSS treatment often led to death of the Mn‐deficient animals (Figure ).…”

“…29 In contrast, rats fed a zinc-deficient diet (5 mg/kg) for 3 weeks showed exacerbation of DSS-induced colitis. 30 In the present study, dietary Mn deficiency worsened the severity of experimental colitis and promoted IBD development in mice after feeding a low Mn diet for only 2 weeks, and the DSS treatment often led to death of the Mn-deficient animals ( Figure 2). Our data underscore the crucial role of dietary Mn in maintaining intestinal mucosal homeostasis and suppressing IBD.…”

Epithelial Transport in Inflammatory Bowel Diseases

“…However, its expression and activity has not been investigated in IBD patients or in experimental models. Recently, Suwendi et al (140) showed that in DSS colitis in rats, serum zinc level was reduced regardless of dietary Zn concentration. Moreover, rats on a zinc-deficient diet showed exacerbated symptoms of colitis with increased TNFa production (140).…”

“…Recently, Suwendi et al (140) showed that in DSS colitis in rats, serum zinc level was reduced regardless of dietary Zn concentration. Moreover, rats on a zinc-deficient diet showed exacerbated symptoms of colitis with increased TNFa production (140). Current knowledge, however limited, suggests that plasma Zn levels should be measured in IBD patients and used as a guide for supplementation with zinc sulfate.…”

Zinc Deficiency is Associated with Poor Clinical Outcomes in Patients with Inflammatory Bowel Disease

“…In animal models, zinc deficiency exacerbates colitis and potentiates production of pro-inflammatory cytokines, including tumor necrosis factor α (TNFα) (7, 8). Furthermore, previous work indicates that a low zinc diet in healthy volunteers results in a decrease in the TH1 cytokines, IFN-γ and IL-2, as well as diminished lytic activity of natural killer cells (2).…”