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Summary
Introduction
Animals
Inbred Wistar albino rats of either sex of approximately the same age,
weighing between 200 230 g, were obtained from the Experimental Animal
Care Center, College of Pharmacy, King Saud University, Riyadh. The rats
were fed standard chow diet (Silos and Flour Mills Organization Feed Mill,
Riyad) and water ad libitum. They were divided into various groups of six to
eight animals each. The distribution of the animals into groups, the sequence
of the trials and the treatment allotted to each group were randomized.
Extract preparation
Turmeric rhizomes were procured from the local market of Riyadh, Saudi
Arabia and identified in the Taxonomy Division of the Medicinal, Aromatic
and Poisonous Plants Research Center of King Saud University, Riyadh. The
powdered drug (500 g) was extracted using a percolation method and 96%
ethanol. The solvent was then removed at low temperature under reduced
pressure and the extracts so prepared were stored in a refrigerator for
pharmacological studies. The extract yield was 9.5% (w/w) in terms of start-
ing material. All doses are expressed here in terms of the extract itself.
Pyloric ligation. The pylorus was ligated according to the method of Shay
et al. (1945) under light ether anaesthesia with care taken not to cause bleed-
ing or to occlude blood vessels. Six hours after ligation, the animals were
killed by an overdose of ether, the stomachs removed, contents collected,
measured for volume, centrifuged and subjected to analysis for titratable
acidity against 0.1 N NaOH to pH 8 using a pH meter. Total acid output was
calculated. Each stomach was examined for lesions in the forestomach por-
tion and indexed according to severity.
Hypothermic-restraint stress-induced ulcers. The method of Levine (1971)
was followed with slight modification. The animals were taken off food for 24
h with access to water ad libitum and 1 h after receiving the corresponding
treatments, they were placed in a metallic restraint cage inside a
refrigerator (24C) for 2 h. They were killed at the end of this period.
Indomethacin-induced ulcers. Ulcers were induced according to the
method of Bhargava et al. (1973). Indomethacin was suspended in 1% carbox-
ymethycellulose in water and administered orally at a dose of 30 mg/kg (5
ml/kg). Six hours after indomethacin administration, the animals were killed.
Reserpine-induced ulcers. The method of Gupta et al. (1974) was followed.
Reserpine (CIBA) was administered in a dose of 5 mg/kg i.m. (5 ml/kg) and
the animals were killed 24 h later.
Cytoprotection studies. The method of Robert (1979) was followed. The
following necrotizing agents were administered orally to male rats in a vol-
ume of 1 ml: 80% ethanol, 0.6 M HC1, 25% NaCl and 0.2 M NaOH. Turmeric
extract (500 mg/kg; 5 ml/kg) or the vehicle alone (normal saline) was given
i.g., 30 min before the necrotizing agents. One hour after the administration
of necrotizing agents, the animals were sacrificed and each was examined for
gastric lesions.
General procedures
The ethanol extract of turmeric (100 mg/ml) was given at a dose of 500
mg/kg p.o. 30 min before the administration of an ulcerogenic agent (twice in
case of reserpine and cysteamine) and at the beginning of stress procedures.
In Shay rats it was administered immediately after pylorus ligation. Control
animals received an equivalent volume (5 ml/kg) of the normal saline vehicle.
The animals were killed at the end of specified periods using anaesthetic
ether and the stomach and duodenum were excised. The duodenum was
opened along its anti-mesenteric side and the stomach along the greater cur-
vature, their contents were rinsed off with saline and the linings examined
with a 6.4 X binocular magnifier. Lesions were assessed by two observers
unaware of the experimental protocols.
Gastric lesions induced by all the procedures used in this study were mul-
tiple in each stomach. They were evaluated singly according to their dimen-
sions and severity, and scored using a scale of 0 (no visible ulcers) to 10 (deep
lesions with a diameter greater than 8 mm in each stomach). The scores for
each single lesion were then summed so that the total score per stomach
could exceed the value of 10 (Tariq et al., 1985).
The duodenal ulcers were scored for intensity, using a scale of 0 to 3,
where 0 = no ulcer, 1 = superficial mucosal erosion, 2 = deep ulcer or
transmural necrosis, 3 = perforated or penetrated (into the pancreas or
liver) ulcer (Szabo, 1978). The ulcer index is the sum of the arithmetic mean
of the intensity for a group and the ratio of positive/total multiplied by 2,
e.g. 2.1 + (9/10 X 2).
29
The results refer to the average lesion score S.E.M. Statistical analysis
of the severity of gastric ulcers was done by Student's t-test.
Results
TABLE 1
TABLE 2
Hypothermic-restraint stress
Control 6 26.5 2.3
Turmeric 6 500 X 1 17.2 + 2.4*
Indomethacin
Control 6 35.2 1.6
Turmeric 6 500 X 1 23.3 3.1***
Reserpine
Control 6 37.0 2.0
Turmeric 6 500 X 2 18.0 3.1***
Cysteamine
Control 7 1.85 0.26
Turmeric 7 500 X 2 1.00 0.37
Significance relative to respective control data: *P < 0.05, **P < 0.01. ***P < 0.001.
TABLE 3
Normal 7
_ 305 24* < 0.001
(unstressed)
Control 7 196 9
(stressed)
Turmeric 7 500 385 31* < 0.001
(stressed)
TABLE 4
TABLE 5
Discussion
The results of this study clearly indicate that the oral administration of an
ethanol extract of turmeric produced significant anti-ulcer and cytoprotec-
tive effects in rats. Hypothermic-restraint stress ulcers have been widely
used experimentally for the evaluation of anti-ulcer activity in rats because
of data reproducibility (Murakami et al., 1985). Disturbances of gastric
mucosal microcirculation (Guth, 1972), alteration of gastric secretion (Kita-
gawa et al., 1979) and abnormal gastric motility (Watanabe, 1966) have been
considered to be the pathogenic mechanisms responsible for stress-induced
gastric mucosal lesions and gastric mucus depletion (Koo et al., 1986). The
increase in gastric acid secretion is considered to be an important factor in
the genesis of stress ulcer and is often termed as the "aggressive factor"
(Goa and Monk, 1987). The antisecretory activity of turmeric as observed in
our Shay rat model might be important in protecting gastric mucosa against
stress-induced ulceration.
Turmeric has been shown to possess highly significant antioxidant activity
and Toda et al. (1985b) have shown that the methanol extract of turmeric
possesses better anti-oxidant properties than a-tocopherol. Young et al.
(1976) found that a-tocopherol can mitigate stress-induced ischemia in tissues.
Our findings are in agreement with earlier authors who reported significant
anti-ulcer activity for a number of other anti-oxidants including superoxide
dimutase, vitamin E, selenium and AT-acetylcysteine (Javor et al., 1986; Par-
mar et al., 1988; Tariq, 1988). The ability of turmeric extract to produce a
significant reduction of the gastric mucosal damage induced by indomethacin
32
Acknowledgement
The authors are thankful to the King Abdulaziz City for Science and Tech-
nology (KACST) for financial support.
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