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


OBJECTIVE
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.


CONCLUSIONS
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.
Carrier
Julie C
JC
Department of Medicine, University of Toronto, Toronto, Ontario, M5G-2C4, Canada.
Aghdassi
Elaheh
E
Jeejeebhoy
Khursheed
K
Allard
Johane P
JP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D016264:Dextran Sulfate; D019587:Dietary Supplements; D004195:Disease Models, Animal; D007202:Indicators and Reagents; D007501:Iron / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014131:Trace Elements / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D016207:Cytokines; D007202:Indicators and Reagents; D008054:Lipid Peroxides; D016328:NF-kappa B; D014131:Trace Elements; D014810:Vitamin E; D016264:Dextran Sulfate; D007501:Iron; D009195:Peroxidase