This document describes several models used to study anti-ulcer drugs: the pylorus ligation model in rats, immobilization stress model, cold water immersion stress model, and indomethacin-induced ulcer model. For each model, it provides details on the purpose, procedures, evaluation methods, and critical assessments. The pylorus ligation and immobilization stress models are used to study drugs with various mechanisms of action and resemble factors in human ulcer pathogenesis. The cold water and indomethacin models are described as useful for final drug evaluation but may not be fully inhibited by H2 receptor antagonists.

1. SHAISTA AHMED
M.SC. CLINICAL
RESEARCH (SEM-I)
JAMIA HAMDARD
ANTI-ULCER MODELS

2. CONTENT
Introduction
Method of intermittent observations.
Hole-board test
OPEN FIELD TEST
SABBU ISKO EDIT KR DIO MRA DKH K
PLEASE.

3. ULCER
An ulcer is a sore area on the outside or
inside of your body caused by a break in skin
or mucous membrane which fails to heal.

4. PYLORUS LIGATION IN RATS(SHAY
RATS)
PURPOSE AND RATIONALE
 The pylorus part of the stomach is ligated
It causes ulcers in rats by stopping the passage of
gastric content from stomach and accumulation of
acidic gastric juice in the stomach for longer time

5. PROCEDURE
Wistar male rats was taken of 180-200g and was kept
for fasting for 48hrs.Under anesthesia 1 inch
abdominal incision is given.
Pylorusis ligated without damaging blood supply,test
compound given orally or injected.
About 17-19hrs of ligation rats are sacrificed and
stomach dissected out. The content of stomach are
drained into centrifugation tube and send for study
Stomach inner surface examined for ulceration under
ocular microscope and ulcer index is calculated and
severity is marked.

6. EVOLUTION OF RESULTS
The number of ulcer is noted and severity
recorded with following scores
0=no ulcer
1=superficial ulcer
2=deep ulcer
3=perforation
An ulcer index UI is calculated
UI=UN+US+UP*10-1
UN=average of number of ulcer per animal
US=average of severity scores
UP=percentage of animal with ulcers

7. CRITICAL ASSESSMENT OF THE
METHOD
The shay-rat has been proven to be valuable tool
to evaluate anti-ulcers drug with various
mechanism of action.

8. STRESS-ULCER THROUGH
IMMOBILIZATION STRESS
PURPOSE AND RATIONALE
Psychogenic factor such as stress plays a major
role in the pathogenis of gastric ulcer in man.
Hanson and Brodie in 1960 described method to
study the effects of anti-ulcers drug on
immobilization stress in rats.

9. PROCEDURE
Group of 10 females wistar rats weighing 150-
170g are used, food and water are withdrawn
24hrs before experiment.
After oral or subcutaneous administration of
compounds the animals are anesthetized by ether
and both lower and upper extremities are fixed
together and animals wrapped in wire gaze.
They are horizontally suspended in dark at 20 c
for 24hrs and finally sacrificed in co2
anesthesia,the stomach removed and fixed on a
cork plate
Ulcer index and ulcer severity is determined with
a stero-microscope.

10. EVALUATION OF RESULTS
 The number of ulcer is noted and severity
recorded with following scores
 0=no ulcer
 1=superficial ulcer
 2=deep ulcer
 3=perforation
 An ulcer index UI is calculated
 UI=UN+US+UP*10-1
 UN=average of number of ulcer per animal
 US=average of severity scores
 UP=percentage of animal with ulcers

11. CRITICAL ASSESSMENT
The experimental model resembles the
psychogenic factors in the pathogenesis of gastric
ulcers in patients.
Psychotropic drugs like neuroleptics have been
found effective in this test..

12. STRESS ULCER BY COLD WATER
IMMERSION
PURPOSE AND RATIONALE
Cooling of rats in water during restraint period
accelerates the occurrence of gastric ulcers and
shorten time of necessary immobilization.

13. PROCEDURE
Groups of 8-10 wistar rats weighing 150-200g are
used. After administration of test compounds rats are
placed vertically in restraint cages in water at 22.c for
1 hour.
They are removed dried and injected intravenously via
tail with 30mg/kg Evans blue.10 mins later they are
sacrificed in co2 anesthesia and stomach is removed.
Formolsaline is then injected to the totally ligated
stomach for storage overnight.
The next day stomach opened washed in warm water
and examine under 3-fold magnifier.
The length of the longest diameter of the lesions are
measured,the mean out of each group being
calculated.

14. EVALUATION
The mean score in control rate is about
25.Inhibition of the lesion production expressed as
percentage value.

15. CRITICAL ASSESSMENT OF THE
METHOD
It resembles the psychogenic factor for ulcer
disease in human beings, is used for final drug
evaluation only.

16. INDOMETHACIN INDUCED ULCERS IN
RATS
• Nonsteroidal anti-inflammatory agents like
indomethacin and acetyl salicylic acid induce
gastric lesions in man and experimental
animals by inhibition of gastric cyclo-
oxygenase resulting in less formation of
prostracyclin,the predominant prostranoid
produced in the gastric mucosa.

17. PROCEDURE
• Group of 8-10 wistar rats weighing 150-200g
are used.The test drug administered orally
10 min prior to oral indomethacin in a dose of
20mg/kg.
• Six hours later rat are sacrificed in co2
anesthesia and their stomach removed.
• Formal-saline is then injected into the totally
ligated stomach for storage overnight
• The next day stomach are open and washed
in warm water and examined under a 3-fold
magnifier.

18.  The lengths of the longest diameters of the
lesions are measured and summated to give a
total lesion score(in mm) for each animal and
mean is calculated.

19. EVALUATION
• The mean score in control rats is about
25(20-28).Inhibition of the lesion production
is expressed as percentage volume.

20. CRITICAL ASSESSMENT OF THE
METHOD
• According to West (1982) the cold stress
induced ulcer formation, but not the
indomethacin-or aspirin-induced ulcers are
inhibited by h2 receptor antagonists, whereas
others authors reported protective effects of
H2 receptor antagonists under these
condition.

21. Thank you