A brief outline with description of various methods to induce ulcer in experimental animals

1. Anti-Ulcer Screening of Drugs
Methods with short descriptions
S K KANTHLAL
Amrita School of Pharmacy
Kochi

2. Anti Ulcer DrugsAnti Ulcer Drugs
1. Pylorus Ligation (SHAY RAT)1. Pylorus Ligation (SHAY RAT)
2. Stress Ulcer Model2. Stress Ulcer Model
a) Restrained induced ulcer (restrained Animal)a) Restrained induced ulcer (restrained Animal)
b) cold-restraint stress (cold water immersion induced ulcer)b) cold-restraint stress (cold water immersion induced ulcer)
c) Swimming stress ulcerc) Swimming stress ulcer
3. Induced Ulcers3. Induced Ulcers
a) Histamine Induced Gastric Ulcersa) Histamine Induced Gastric Ulcers
b) Ethanol induced mucosal damageb) Ethanol induced mucosal damage
c) Acetic acid induced Gastric ulcersc) Acetic acid induced Gastric ulcers
d)d) Cysteamine Induced Duodenal UlcersCysteamine Induced Duodenal Ulcers
f) Dimaprit Induced Duodenal Ulcersf) Dimaprit Induced Duodenal Ulcers
g) NSAIDsg) NSAIDs (indomethacin, aspirin, and ibuprofen)(indomethacin, aspirin, and ibuprofen) induced gastric ulcersinduced gastric ulcers

3. Model Animal Method Observation
Restrained model Albino Rats
Both sex
Fasting: 36
hrs
Apparatus: Specialized
Galvanized steel apparatus
Tie all the limbs (in pair) in a
galvanized steel window screen.
(24 hrs)
Test drug: 30 min before
experiment
Total Acidity, Free
acidity
Ulcer Index (after
Sacrifice)
Cold-restraint stress:
Restrained animal
when subjected to
cold water
immersion,
increases the stress
& accelerates GI
ulcer
Wistar rats
Fasting: 16
hrs
Individually placed in restrained
cages
Administer oral test drug
Immersed in water (22°C for I hr)
Evan's blue (3m mg/kg) in tail
vein
Stomach removed,
kept in formalin
over night
Examine the ulcer
lesion (color)
calculate the score
Less longest-->
more the protection
Stress Ulcer Model
The involvement of psycogenic factors in production of ulcers

4. DISECTED
AND
PINNED
STOMACH

5. Model Animal Method Observation
Swimming stress Albino Rats
Both sex
Fasting: 24
hrs
Test drug orally
Deep concrete tube filled
with water (23°C)
Allow to swin for 5 hrs
Total Acidity, Free acidity
Ulcerative lesions:
0- no
1- dia less < 1mm
2- dia 1-2mm
3- dia 2-4mm
4- dia >4 mm

6. Model Requirements Method Observation
Histamine
model
(H2 Recep
activation)
Male Guinea Pig
(300-400gm)
Histamine
sulphate: 50 mg i.p
Fasting: 36 hrs
Test drug administered
After 30-45 min → ip ing of
Hist
Promethazine Hcl 5 mg 15 min
before and after Histamine
Leave for 4 Hrs
Total Acidity, Free
acidity
Ulcer Index
Ethanol model
for Mucosal
damage
Absolute
ethanol in
fasted animal
for I hr induces
gastric lesion)
Wistar rats
Fasting: 18 hrs
Test drug administered
After 30 min 1 ml oral ethanol
provided
Stomach removed,
total acidity,
Tissues observed
under light
transmission
densitometer
Lower the density
→ higher the
damage
Chemical Induced Ulcers

7. Model Requirements Method Observation
Acetic acid
(Chronic model for
both gastric/duodenal
ulcer)
Albino rats
Cysteamine in DU
(↓ Mucous production,
↑Gastrin, gastric acid
& delays GET)
Model for A- Ach,
antacids, PG's, H2
antagosi
Female SD rats
Cysteamine Hcl
(10% in NS)
28mg/100gm – 3times at
3.5 hrs orally or 20
mg/100gm 2 times at 4
hrs sc
Sacrifice: 28 hrs after cyst
Perforating ulcers
in the anterior wall
of duodenum
Necrosis is
observed an
compared
Dimaprit
Hist 2 Selective
agonist
Suitable for H2
blocking effect
Female SD rats
Female Gps
Dimaprit:
100mg/kg
Fasting: 24 Hrs
Rats: single iv ing
Test: 60 min before
Dimaprit
Gps: 2 mg/kg every hr for
6Hr
Test: 30min before 1st
dose
Dissected after 1
hr.
Stomach/duodenu
m examined for
gastric erosion
Acidity may be ...?