Expt. 5 Study of anti ulcer activity of a drug using nsaid induced ulcer model

Mr. Vishal Balakrushna Jadhav
Assistant Professor (Pharmacology)
GES’s Sir Dr. M. S. Gosavi COPER, Nashik-5
ExperimentNo. 5
Study of anti-ulcer activity of a drug
using NSAID induced ulcer model
1

• Objective
• Principle
• Requirements
• Preparation of drugs solution.
• Procedure
• Observation table
• Result and Interpretation
Overview of Discussion
2

To study antisecretory and ulcer protective effect of
ranitidine/cimetidine using NSAIDs inducedulcers in rat.
Objective
3

Peptic ulcers are the areas of degeneration and necrosis of
gastrointestinal mucosa exposed to acid-pepsin secretions.
Though the ulcers can occurs at any site of the alimentary
tract exposed to hydrochloric acid and pepsin, peptic ulcers
can occurs most commonly in either duodenum or stomach.
The imbalanced secretions of gastric acid, pepsin and duodenal
mucosal defense mechanisms are the causes of such ulcers.
Excessive non-steroidal anti-inflammatory drugs (NSAIDs)
consumption can cause damage of gastrointestinal mucosa
leading to ulcers. NSAIDs are most commonly used
medications in the developed countries and are responsible
for direct toxicity, endothelial damage and epithelial injury to
both gastric and duodenal mucosa.
Principle
4

NSAIDs which induces development of gastric ulcers are aspirin,
indomethacin, phenylbutazone, ibuprofen etc. Inhibition of
endogenous prostaglandin production leads consequent loss
of gastric mucosal defense, which in turns causes the
formation of ulcer.
It is important model for identifying drugs that could be effective
in NSAID induced gastropathy.
5

Animals Albino Wistar rats of (200-300g), either sex (M/F)
Drugs Aspirin (500 mg/kg, p.o.), phenylbutazone (100 mg/kg,
p.o.), Indomethacin (20 mg/kg, p.o.), Cimetidine (10 mg/ kg,
i.p. Prepare a stock solution containing 2 mg/ml of the drug
and inject 0.5 ml/ 100 g body weight of the animal) or
Ranitidine (20 mg/kg, p.o.).
Chemicals 1% Carboxy methylcellulose (CMC), Tween 80, 0.9 %
normal saline solution.
Instruments Dissecting microscope (10X magnification), Surgical
instruments.
Requirements
6

Aspirin Aspirin is suspended in 1% CMC in water (20mg/ml) and
administered the drug with a dose of 500 mg/kg, p.o.
Phenylbutazone It is administered in a similar fashion as aspirin in
a dose of 100mg/kg, p.o. (suspension) or i.p.(solution).
Indomethacin Indomethacin is administered in a dose of 20mg/kg
(4mg/ml dissolved in 0.1% Tween 80 solution) p.o.
Preparationof Drugs Solution
7

 Select albino rats weighing 200-300 g and divide them into two
groupsconsisting of 3 animals in each group.
 Group-1 (control group) receives 1% CMC. Group-2 (drug treated
group) receives Cimetidine (10 mg/ kg, i.p.) or Ranitidine (20
mg/kg, p.o.) daily for 2 days and 30 mins prior to administration of
ulcerogenicagent(NSAIDs).
 Administer aspirin (500 mg/kg, p.o.) or phenylbutazone (100
mg/kg, p.o.) or Indomethacin (20 mg/kg, p.o.) after 30 minutes of
antiulcer drug administration in both groups. Avoid access to
feedand water to animals.
 After 6 hours sacrifice the animals by cervical decapitation. Open
the abdomen and tie the esophageal end (cardiac end) of the
stomach. Cut and remove the entire stomach from the body of
the animal.
 Give a small cut to the pyloric region just above the knot and
collect the contents of the stomach in a graduated centrifuge
tube.
Procedure
8

 Open the stomach along the greater curvature and wash it slowly
under the running tap water or with 0.9% saline. Put it on the glass
slide and observe under 10X magnification for ulcers. Score the
ulcers as below-
Intensity of ulcers with scoring-
 0 – normal coloration;
 0.5 – red coloration;
 1 – spot ulcer;
 1.5 – hemorrhagic streaks (bands)
 2 – deep ulcer (ulcer count ≥ 3 but ≤ 5)
 3 – perforations (ulcer count > 5)
 Mean ulcer score for each animal is expressed as ulcer index.
9

 Analysis of stomach contents- Centrifuge the gastric content at 1000
rpm for 10 minutes. Note the volume. Pipette out 1 ml of supernatent
liquid and dilute it to 10 ml with distilled water. Note the pH of this
solution with the help of pH meter. Titrate the solution against 0.01 N
NaOH using Topfer’s reagent as indicator. (Topfer’s reagent is
dimethylaminoazobenzene with phenolphthalein and used for
detection and estimation of HCl and total acidity in gastric fluids).
Titrate to the end point when the solution turns to orange colour. The
volume of NaOH used is to be noted to estimate free acidity. Titration
has to be continued till the appearance of pink colour and the volume
of NaOH run down is to be noted to calculate total acidity. Acidity
(mEq/l/100 g) can be expressed as-
 Compare the gastric volume, acidity and ulcer index of control animals
and the animals treated with cimetidine/ ranitidine.
 Report the readings in observation table. Interpret and conclude the
result. 10

Sr. No. Treatment
Dose
(mg/kg,
i.p./p.o.)
Volume
of gastric
content
(ml)
pH
Acidity(mEq/l
/100 g) Ulcer
Index
Free Total
1
Control*
2
3
Cimetidine*
4
5
Ranitidine*
6
Observation table
11
*6Hours after drug administration

 Comparison of ulcer index between study groups estimates
the potency of antiulcer activity of test drug. Decrease in
volume of gastric contents, free and total acidity
determines antisecretory activity of test drug and rise in pH
evaluates acid neutralizing action of the drug.
 Cimetidine/ Ranitidine reduces gastric acid secretion and
inhibits ulcer formation in NSAIDs treated animals.
Result and Interpretation
12

Expt. 5 Study of anti ulcer activity of a drug using nsaid induced ulcer model

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Expt. 5 Study of anti ulcer activity of a drug using nsaid induced ulcer model