An ulcer is a local defect, or excavation of the surface of an organ, or tissue, which is produced by the sloughing of inflammatory necrotic tissue. The term ‘peptic ulcer’ refers to a group of ulcerative disorders of the upper GIT, which appears to have in common, the participation of acid pepsin in their pathogenesis. A peptic ulcer probably results due to an imbalance between aggressive (acid, pepsin, and H. pylori) and defensive (gastric mucous, bicarbonate secretion, prostaglandins, innate resistance of the mucosal ceils) factors. In gastric ulcers, acid secretion is normal or low.
SCREENING METHODS FOR ANTIULCER AGENTS
An ulcer is a local defect, or excavation of the surface of
an organ, or tissue, which is produced by the sloughing of inflammatory
necrotic tissue. The term ‘peptic ulcer’ refers to a group of ulcerative
disorders of the upper GIT, which appears to have in common, the participation
of acid pepsin in their pathogenesis. A peptic ulcer probably results due to an
imbalance between aggressive (acid, pepsin, and H. pylori) and defensive
(gastric mucous, bicarbonate secre-tion, prostaglandins, innate resistance of
the mucosal ceils) factors. In gastric ulcers, acid secretion is normal or low.
Pylorus Ligation in Rats
This principle is based on ulceration induced by
accu-mulation of acidic gastric juice in the stomach (Shay et al. 1945).
The requirements include: stereo microscope, adult albino
rats (150–170 g), anaesthetic ether, plastic cylinder, 0.1 N sodium hydroxide.
Adult albino rats weighing 150–170 g are starved for 48 h
although they have access to drinking water. Normally ten animals are used per
dose and as control. After they are ether anaesthetized, a midline abdominal
incision is made and the pylorus ligated. The abdominal wall is closed by
sutures and test compounds are given either orally by gavage or injected
subcutaneously. The animals are placed for 19 h in plastic cylinders with an
inner diameter of 45 mm being closed on both ends by a wire mesh. The animals are
then sacrificed using carbon dioxide anaesthesia. The abdomen is opened, and a
ligature is placed around the aesophagus close to the diaphragm. The stomach is
removed and the contents drained into a centrifuge rube. Along the greater
curvature, the stomach is opened and pinned onto a cork plate. The mucosa is
then examined with a stereo microscope.
The evaluation is done by counting the numbers of ulcers and
the severity graded according to the following scores:
0 = no ulcers; 1 = superficial ulcers; 2 = deep ulcers; 3 =
perforations
The volume of gastric content is measured after
cen-trifugation. Acidity is determined by titration with 0.1 N NaOH. Ulcer
index U is calculated using the
following formula:
U1 = Un + Us + Up × 10–1
where Un
= the average number of ulcers per
animal, Us = average of
severity score, and
Up = percentage of animals with ulcers
Ulcers Through Immobilization Stress
The principle behind this method involves psychogenic
factors, such as stress, which play a major role in the pathogenesis of gastric
ulcers in man.
The requirements include: adult albino rats, anaesthetic
ether, CO2 anaesthesia, and a stereo microscope.
A group of 10 adult albino rats (150–170 g) per dose of the
test drug and for controls are used. Food and water are withdrawn 24 h before
the experiment. After oral and sub-cutaneous administration of the test
compound or a placebo solution, the animals are slightly anaesthetized with
ether. Both the upper and lower extremities are fixed together and the animals
wrapped in wire gauge. They are horizontally suspended in the dark at 20°C for
24 h and finally sacrificed using carbon dioxide anaesthesia. The stomach is
removed, fixed on a cork plate, and the number and severity of the ulcers
registered with a stereo microscope.
Stress Ulcer by Cold Water Immersions
The principle behind this assay is that cooling the rats in
water when they are restrained according to the previous model accelerates the
occurrence of gastric ulcers and shortens the time of necessary immobilization.
In this model, the gastric ulcer formation is mainly due to gastric
hypermotility, which could lead to mucosal over-friction.
The requirements include: wistar rats, cages, Evans blue
dye, 2% formol saline, CO2 anaesthesia, and a magnifier.
Groups of 8–10 wistar rats weighing 150–200 g are used.
After oral administration of the test compounds, the rats are placed vertically
in individual restraint cages in water at 22°C for 1 h. They are then removed,
dried, and injected intravenously through a tail vein with 30 mg/ kg Evans
blue. After 10 min, they are sacrificed using CO2 anaesthesia and
their stomachs removed. Formol saline (2% v/v) is then injected into the
totally ligated stomachs for storage overnight. The next day, the stomachs are
opened along the greatest curvature, washed in warm water, and examined under a
threefold magnifier.
The evaluation is done by measuring the lengths of the
longest diameter of the lesions. This is summated to give a total lesion score
(in mm) for each animal; the mean count in control rats should be about 25
(range 20–28). Inhibition of the lesion production is expressed as a
per-centage value.
Indomethacin-induced Ulcers in Rats
This assay is based on the fact that use of nonsteroidal
anti-inflammatory agents like indomethacin and acetyl salicylic acid induces
gastric lesions in man and in experimental animals by inhibition of gastric
cyclooxygenase.
The requirements include: wistar rats, 0.1% tween 80, 2%
formol saline, and CO2 anaesthesia.
Groups of 8–10 wistar rats weighing 150–200 g are used. The
test drugs are administered orally in 0.1% tween 80 solutions 10 min before an
oral administration of indo-methacin (20 mg/kg). After 6 h, the rats are
sacrificed in CO2 anaesthesia and their stomachs removed. Formol
saline (2% v/v) is then injected into the totally ligated stomachs for storage
overnight. The next day, the stomachs are opened along the greatest curvature,
washed in warm water, and examined.
The mean score is calculated in control rats. It should be
about 25 (range 20–28). Inhibition of the lesion production is expressed as a
percentage value.
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