Effects of iron deprivation or chelation on DNA damage in experimental colitis.
OBJECTIVE
In inflammatory bowel diseases iron contributes to the formation of DNA adducts through the production of hydroxyl radicals. The aim of our study was to evaluate the effects of dietary or pharmacological iron deprivation in an experimental model of colitis in the rat and its potential protective effect against DNA damage.


METHODS
Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulphonic acid. Rats were assigned to an iron-deprived diet or to desferrioxamine preceding the induction of colitis. The severity of colitis was assessed by the presence of bloody diarrhea, colonic macroscopic damage score, body-weight variations and the amount of DNA colonic adducts. Hepatic and colonic iron concentrations were measured.


RESULTS
Treated rats experienced less diarrhea and did not lose weight in comparison to untreated animals. The macroscopic damage score was significantly reduced in the iron-deprived diet for the 5-week group (P=0.03). Liver and colonic iron levels were significantly more reduced in the iron-deprived groups than in the standard diet group (P<0.03 and P<0.01 after a 3- and 5-week iron-deprived diet, respectively). DNA adduct formation was significantly reduced in the groups deprived of iron for 5 weeks (P<0.001) or treated with desferrioxamine (P<0.01).


CONCLUSIONS
The degree of colitis caused by DNBS is macroscopically improved by dietary iron deprivation and to a lesser extent by pharmacological chelation; genomic damage is reduced by dietary iron deprivation or chelation, and this may have clinical implications on cancer prevention.
Barollo
M
M
Department of Surgical and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, Padova, Italy.
D'Incà
R
R
Scarpa
M
M
Medici
V
V
Cardin
R
R
Fries
W
W
Angriman
I
I
Sturniolo
G C
GC
D000818:Animals; D003092:Colitis / Q000235:genetics* / Q000503:physiopathology*; D018736:DNA Adducts; D004249:DNA Damage; D003676:Deferoxamine / Q000494:pharmacology*; D003967:Diarrhea / Q000209:etiology / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D007501:Iron / Q000009:adverse effects* / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D015431:Weight Loss
D018736:DNA Adducts; D007502:Iron Chelating Agents; D007501:Iron; D003676:Deferoxamine