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SCREENING METHODS OF ANTIULCER AGENTS

SUBMITTED BY: ANUSHA KATYAYANI .Y Ist M.Pharm PHARMACOGNOSY

ULCER:
Gastric hyperacidity and gastroduodenal ulcers are

very common global health problems today. A lesion of the skin or of a mucous membrane or a localised erosion in stomach or duodenum, that is accompanied by formation of pus and necrosis of surrounding tissue, usually resulting from inflammation or ischemia. Peptic Ulcer - a broad term for an ulcer occurring in the esophagus, stomach, or duodenum or with in the upper GI tract (esophageal, gastric & duodenal ulcers).

ULCER:

PARAMETERS CONSIDERED
Inhibition of gastric acid secretion
Promoting gastroprotection Blocking apoptosis

Stimulation of epithelial proliferation

MODELS: gastric ulcer models


Pylorus ligation in rats Stress models Stress ulcer through immobilization stress

Stress ulcers by cold water immersion


Indomethacin induced ulcers in rats Ethanol induced mucosal damage in

rats(cytoprotective activity)

PYLORUS LIGATION IN RATS


In this method the ulceration is caused by accumulation of

acidic gastric juice in the stomach. published by Shay et al. in 1945. PROTOCOL: Female Wistar rats weighing 150170 g are starved for 48 h having access to drinking water. Ten animals are used per dose and as controls. Under ether anesthesia a midline abdominal incision is made and the pylorus is ligated. The abdominal wall is closed by sutures. The test compounds are given either orally by gavage or injected subcutaneously.

After 17-19 h the animals are sacrificed. Stomach is removed and the contents are drained in a centrifuge

tube. Along the greater curvature the stomach is opened and pinned on a cork plate. The mucosa is examined with a stereomicroscope. Lesions occur mainly in the rumen and in the antrum. The number of ulcers is noted and the severity recorded with the following scores: 0 = no ulcer 1 = superficial ulcers 2 = deep ulcers 3 = perforation. The volume of the gastric content is measured. After centrifugation, acidity is determined by titration with 0.1 n NaOH.

STRESS ULCER THROUGH IMMOBILIZATION STRESS


Published by Selye ,Hanson and Brodie and Bonfils et al. The principple behind this method involves pcychogenic factors,such as stress,which play a major role in the pathogenesis of gastric ulcers in man.

PROTOCOL: 10 female Wistar rats weighing 150170 g are used and kept for fasting for 24 h After oral or subcutaneous administration of the test compound, they are anasthetised Both lower and upper extremities are fixed together and the animals are wrapped in wire guaze. They are horizontally placed in the dark at 20 C for 24 h and sacrificed. The stomach is removed, and the number and severity of ulcers is noted with a stereo-microscope using the following scores: 0 = no ulcer 1 = superficial ulcers 2 = deep ulcers 3 = perforation

STRESS ULCERS BY COLD WATER IMMERSION


Takagi et al. in1964 The principle behind this assay is that cooling the rats in water when they

are restrained according to the previous model accelerates the occurrences of gastric ulcers and shortens the time of necessary immobilisation . In this model,the gastric ulcer formation is mainly due to gastric hypermotility , which could lead to mucosal over-friction. PROTOCOL: Groups of 810 Wistar rats weighing 150200 g are used. Oral administration of the test compound, placed vertically in individual restraint cages in water at 22 C for one hour. Then, removed, dried and ten min later, sacrificed and stomachs are removed and stored in Formolsaline(2% v/v) overnight. The next day, the stomachs are opened, washed in warm water, and the lengths of the longest diameters of the lesions are measured and summated to give a total lesion score (in mm) for each animal, the mean count for each group is calculated.

INDOMETHACIN INDUCED ULCERS IN RATS


This assay is based on the fact that use of non-steroidal

anti-inflammtory agents like indomethacin and acetyl salicylic acid induces gastric lesions in man and in experimental animals bt inhibition of gastric cyclooxygenase. Groups of 810 Wistar rats weighing 150200 g are used, kept fasting for 24h. The test drugs are administered orally in 0.1% Tween 80 solution 10 min prior to indomethacin. Oral indomethacin in a dose of 20 mg/kg (4 mg/ml dissolved in 0.1% Tween 80 solution). Six hours later, the rats are sacrificed stomachs are removed and stored in Formol-saline (2% v/v) overnight

ETHANOL INDUCED MUCOSAL DAMAGE IN RATS


Published by Robert et al. in 1979

PROTOCOL: Male Wistar rats weighing 250300 g are kept fasting for 18 h prior to the experiment. Administer cytoprotective drug, e.g. a prostanoid, intragastrally 30 min prior to administration of 1 ml absolute ethanol. Untreated animals are included as controls. After one hour , the animals are sacrificed and the stomachs are dissected out and and severity of ulcer is examined and compared between control and test

Evaluation
A light transmission densitometer is used to evaluate

the negatives and the optical density is determined. Evaluation is done by observing haemorrhagic or damaged ares that appears bright on negatives,undamaged appear as dark areas.

REFERENCES:
Herbal drug technology , screening methods for anti-

ulcer activity pg 588-590. Wikipedia,article-gastric ulcer and screening of biological methods.