Aim of experiments: The aethiology of Crohn Disease (CD) despite intensive investigations
remained unknown, therefore its therapy is unsolved. Chronic administration of non-steroidal
anti-inflammatory drugs in humans or single administration of these drugs in experimental
animals provoke ulcerative-inflammatory processes which are similar to CD. The change
of the intestinal permeability may play a role in the aethiology of CD.
Methods: In our experiments rats (Male Wistar rats weghing 250–300g) were treated by indometacin
in a daily dose of 7.5, 10 and 16mg/kg subcutaneously (s.c.) for three days. One day
after the last dose of indometacin the changes in the intestinal tract were analysed
under urethane (1.2g/kg intraperitoneally) anaesthetized rats. Indometacin induced
small intestinal and colonic ulcerations in a dose-dependent fashion. On the base
of the number, dimension and the severity of changes (ulcertion, bleeding, hyperemia)
found in intestinal tract, the effect of indometacin have been classified in five
(0–5) stadiums. For a more precise analysis tissue specimens were taken out from different
segments of the intestinal tract to prepare histological sections for histological
investigation and evaluation.
To study the possible inhibition of the inestinal inflammatory action of indometacin,
mesalazin (5-amino salicylic acid) and steroids (prednisolone, methylprednisolone)
were administered in the following doses: prednisolone: 0.5mg/kg orally, methylprednisolone:3.5mg/kg
intraperitoneally once or twice per day for three days;mesalazin:1g/kg orally once
or twice per day for three days. To investigate the permeability of the intestinal
tract, polyethyleneglycol-400(PEG-400) was administered (3.5g/kg orally) and measured
in the urine by gaschromatograph.
Results and conclusions: Indometacin pretreatment provoked diarrhoea in all cases. Very severe changes in the
middle segment of small intestine were mostly observed. Mucosal ulceration (100%),
mucosal adhesion (40%), mesenterial bleeding (70%), intestinal dilatation (100%) and
thicker intestinal wall have been detected macroscopically. Indometacin given at a
dose of 10mg/kg once a day s.c. for three days produced the most characteristic changes
without severe toxic signs, therefore the results of this type of indometacin treatment
can be considered in our experiments as a good inestinal inflammatory model, which
basically corresponds to CD. Orally given prednisolone was ineffective. Mesalazin
and methylprednisolone produced a protective effect: the severity of inflammation
became less significant (from stadium 3–4 to 0–2;histological analysis supports these
observations, as well), the changes of intestinal permeability also became less significant.
