Exacerbation of dextran sulfate sodium-induced colitis by dietary iron supplementation: role of NF-kappaB

Abstract

Background: In colitis, iron therapy may be given to treat anemia, but it may also be detrimental based on our previous studies using a rat model with colitis where iron supplementation increased disease activity and oxidative stress. This effect was partially reduced by an antioxidant.

Aims: The aim of this study was to further evaluate, in rats with dextran sulfate sodium (DSS)-induced colitis, the effect of iron on neutrophilic infiltration, cytokines and nuclear factor kappa-B (NF-kappaB)-associated inflammation and to determine whether the addition of vitamin E would be beneficial.

Methods: Colitis was induced with DSS at 50 g/l in drinking water for 7 days. DSS rats were randomized to the following: DSS, receiving a control, non-purified diet (iron, 270 mg and DL-alpha-tocopherol acetate, 49 mg/kg); DSS+iron (diet+iron, 3,000 mg/kg); DSS+vitamin E (diet+DL-alpha-tocopherol acetate, 2,000 mg/kg); or the DSS+iron+vitamin E. Colonic inflammation, myeloperoxidase activity (MPO), lipid peroxides (LPO), proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6] and NF-kappaB binding activity were measured.

Results: The DSS+iron group showed a significant increase in inflammatory scores, MPO, TNF-alpha, IL-1, LPO and NF-kappaB activity compared to DSS or DSS+vitamin E. The addition of vitamin E to iron (DSS+iron+vitamin E group) significantly reduced the inflammatory scores, TNF-alpha and IL-6. None of the other parameters were affected.

Conclusion: Iron increases disease activity in colitis, and this is associated with oxidative stress, neutrophilic infiltration, increased cytokines and activation of NF-kappaB. This detrimental effect was partially reduced by vitamin E.