Inflammatory bowel disease in rats: bacterial and chemical interaction.
OBJECTIVE
To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis (UC).


METHODS
Male Sprague-Dawley rats (n = 158) were inoculated intrarectally on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b) 100 microL of 6% iodoacetamide (IA) in 1% MC, (c) 200 microL containing 4 x 10(8) colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and by TNF-alpha gene expression.


RESULTS
Findings indicative of UC were seen in the combined treatment (IA + B) as well as the IA continued treatment groups: the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-alpha gene expression was upregulated compared to the control animals.


CONCLUSIONS
The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity.
Hajj Hussein
Inaya-Abdallah
IA
Faculty of Medicine, 110236/41 Riad El-Slaleh, 1107-2020 American University of Beirut, Beirut, Lebanon.
Tohme
Rania
R
Barada
Kassem
K
Mostafa
Mostafa Hassan
MH
Freund
Jean-Noel
JN
Jurjus
Rosalyn A
RA
Karam
Walid
W
Jurjus
Abdo
A
D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D044683:Colon, Descending / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D054308:Enteropathogenic Escherichia coli; D007460:Iodoacetamide; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D007460:Iodoacetamide