Anti-thyroid drugs decrease mucosal damage in a rat model of experimental colitis.
BACKGROUND
Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4+ cells, increased CD8+ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.


METHODS
Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.


RESULTS
All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82 +/- 0.40 versus 0.11 +/- 0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points (P < 0.01).


CONCLUSIONS
Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.
Oren
R
R
Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Maaravi
Y
Y
Karmeli
F
F
Kenet
G
G
Zeidel
L
L
Hubert
A
A
Eliakim
R
R
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D009336:Necrosis; D009195:Peroxidase / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase