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A
Macroscopir damage scores (AU)
7.5
5.0
2.5
0.0
Sham-colitis TNBS
Figure 1 Effect of a 6 wk juvenile ingestion of ferrous (150 mg/kg per day po) vs ferric (150 mg/kg per day po) iron on the inflammatory response at adulthood
to a trinitrobenzene sulfonic acid-induced colitis in mice. A: Macroscopic damage scores in non-inflamed (sham-colitis) and inflamed (trinitrobenzene sulfonic
acid, TNBS) mice; B: Colonic myeloperoxidase (MPO) activity in non-inflamed (sham-colitis) and inflamed (TNBS) mice. Data are expressed as mean ± SE (n = 8 per
group). a P < 0.05 vs TNBS-treated group, b P < 0.01 vs Sham-colitis.
Effects of ferric iron on TNBS colitis
Repeated daily ingestion of ferrous iron (150 mg/kg
per day po - 6 wk) by juvenile mice did not prevent the
induction of a TNBS-induced moderate colitis. In fact,
juvenile ferrous iron daily exposure failed to limit macroscopic
lesions (Figure 1A) in TNBS treated mice. In contrast,
juvenile ferric iron prevented these lesions (Figure
1A) in inflamed mice. Furthermore, while TNBS enema
resulted in an increased MPO activity in controls (2.47
± 0.22 MPO U/mg protein vs 0.91 ± 0.09 MPO U/mg
protein), we did not observe any significant reduction of
MPO activity in mice exposed to a repeated ingestion of
ferrous iron (1.71 ± 0.27 MPO U/mg protein vs 2.47 ±
0.22 MPO U/mg protein in the TNBS group) (Figure
1B). In contrast, the daily exposure of juvenile mice to
the same dose of ferric iron (150 mg/kg per day po - 6
wk) was able to limit the inflammatory response since
MPO activity was significantly lower (P < 0.05) (1.64 ±
0.14 MPO U/mg protein vs 2.47 ± 0.22 MPO U/mg
protein in the TNBS group) (Figure 1B). Furthermore,
we observed that before inducing TNBS colitis (5 wk of
treatment), mice treated with ferrous iron put on significantly
(P < 0.05) less weight than mice treated with ferric
iron and controls (124.6% ± 1.12% and 136.6% ± 1.33
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b
a
7.5
5.0
2.5
0.0
Sham-colitis TNBS
A B Vehicle
Macroscopir damage scores (AU)
7.5
5.0
2.5
0.0
Sham-colitis TNBS
d
b
b
B
MPO activity (U/mg protein)
MPO activity (U/mg protein)
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Ettreiki C et al . Iron prevents colitis and dysbiosis
b
Sham-colitis TNBS
% vs 143.7% ± 2.29 % in control, respectively).
a
Vehicle
Ferric iron (150 mg/kg per day po)
Ferrous iron (150 mg/kg per day po)
Ferric iron (75 mg/kg per day po)
Ferric iron (150 mg/kg per day po)
Figure 2 Effect of a 6 wk juvenile ferric iron administration (75 and 150 mg/kg per day po) on the inflammatory response at adulthood to a trinitrobenzene
sulfonic acid-induced colitis in mice. A: Macroscopic damage scores in non-inflamed (sham-colitis) and inflamed trinitrobenzene sulfonic acid (TNBS) mice; B: Colonic
myeloperoxidase (MPO) activity in non-inflamed (sham-colitis) and inflamed (TNBS) mice. Data are expressed as mean ± SE (n = 8 per group). a P < 0.05, b P < 0.01
vs TNBS-treated group, d P < 0.01 vs Sham-colitis.
d
Ferric iron juvenile supplementation and dysbiosis
We also aimed at determining the dose-response effect of
ferric iron supplementation on the same model of colitis
in mice.
In control animals, the repeated administration of
both 75 and 150 mg/kg per day po (6 wk) of ferric iron
did not result in any alteration of growth, nor did it result
in colonic inflammation or an alteration of the microflora
profile. In fact, weight gain under iron treatment
remained similar whichever species considered (142.7%
± 2.66% for 75 mg/kg per day and 136.6% ± 1.33 % for
150 mg/kg per day vs 143.7% ± 2.29 % in controls). Similarly,
no macroscopic alterations of the gut mucosa have
been observed on mice following either the low or the
high chronic ferric supplementation (Figure 2A). Those
results were correlated to low levels of MPO activity in
the colonic mucosa following exposure to both doses
of ferric iron (1.65 ± 0.21 MPO U/mg protein and 1.58
± 0.11 MPO U/mg protein for respectively 75 and 150
mg/kg per day ferric iron po vs 0.91 ± 0.09 MPO U/mg
protein in controls) (Figure 2B). Daily consumption of
ferric iron by juvenile rodents did not modify the bacte-
2623 June 7, 2012|Volume 18|Issue 21|
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