Exacerbation of dextran sulfate sodium-induced colitis by dietary iron
supplementation: role of NF-kappaB.
Carrier JC, Aghdassi E, Jeejeebhoy K, Allard JP.
Department of Medicine, University of Toronto, Toronto, Ontario,
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.