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.

• Authors: Julie C Carrier, Elaheh Aghdassi, Khursheed Jeejeebhoy, Johane P Allard
• Journal: International journal of colorectal disease (Int J Colorectal Dis) Vol. 21 Issue 4 Pg. 381-7 (May 2006) ISSN: 0179-1958 [Print] Germany
• PMID: 16133010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Cytokines
• Indicators and Reagents
• Lipid Peroxides
• NF-kappa B
• Trace Elements
• Vitamin E
• Dextran Sulfate
• Iron
• Peroxidase

Topics

• Animals
• Antioxidants (pharmacology)
• Colitis (chemically induced, metabolism, prevention & control)
• Cytokines (drug effects, metabolism)
• Dextran Sulfate
• Dietary Supplements
• Disease Models, Animal
• Indicators and Reagents
• Iron (pharmacology)
• Lipid Peroxides (metabolism)
• Male
• NF-kappa B (drug effects, metabolism)
• Neutrophils (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Peroxidase (drug effects, metabolism)
• Random Allocation
• Rats
• Rats, Wistar
• Trace Elements (pharmacology)
• Vitamin E (pharmacology)