COMPARISON OF EFFECTS
OF EXTRACT OF MYRISTICA FRAGRANS AND VERAPAMIL ON THE VOLUME AND ACIDITY OF
CARBACHOL INDUCED GASTRIC SECRETION IN FASTING RABBITS
Muhammad Jan, Farah Faqir, Hamida, Muhammad
Azhar Mughal**,
Department of Pharmacology SMC, Swat, *Department of
Pathology, LRH Peshawar, **Department of Pharmacology Sir Syed Medical
College, Karachi
Background: Peptic ulcer is mostly
produced due to the over production of gastric acid. This study was undertaken
to find out the effects of extract from Myristica Fragrans which contains
documented natural Calcium channel blocker and Verapamil on volume and acidity
of Carbacol induced gastric section. Their effects were also compared to find
out any difference in their efficacy. Methods:
Thirty rabbits of local breed, weighing 1-1.5kg were used. The animals were
kept on fasting for 48 hours, after which the pylorus of each animal was
ligated. Verapamil 10mg/kg, Myristica fragrans 500 mg/kg and Carbachol 600mg/kg body weight were administered intraperitoneally. Results: It was found that extract
from Myristica fragrans reduced the
volume, free and total acidity of gastric secretion, which were statistically
highly significant when compared with Carbachol (P<0.001). Verapamil had
also the same effects. When the difference of mean for verapamil was compared
with that of extract, all these differences were found statistically non
significant indicating that extract has similar effect as that of Verapamil on
all parameters included in study. Conclusion:
The effect of Myristica Fragrans is similar to Verapamil and therefore it can be
used effectively in the treatment of peptic ulcer and all other conditions that
require calcium channel blockers for the treatment of these disorders.
Keywords: Myristica Fragrans,
Verapamil, gastric acid secretion, Medicinal plant
INTRODUCTION
Peptic ulcer is one of
the most common ailments, with which a physician comes across in the clinical
practice. Increased acid production from gastric mucosa is responsible for
peptic ulceration in majority of the patients. Ulcers are not found in
achlorhydric patients and almost always occur in patients with Zollinger
Ellison (Z.E) syndrome which is characterized by very high acid secretion.1
Inhibition of over production of acid is a desirable therapeutic goal in the
treatment of peptic ulcer. It has been documented that 38 medicinal plants
including Myristica fragrans have natural calcium channel blocker activity.2,3 The calcium channel blocking agents like
Verapamil, nifedipine and diltiazem are commonly used in the treatment of
hypertension, angina, myocardial infarction and supraventricular tachycardia.4
Induction of
hypercalcaemia through intravenous administration of calcium is usually
associated with increased gastric volume and acidity.5,6 The acid
stimulating ability of calcium; is well known and there is extreme sensitivity to calcium in patients
with ZE syndrome.7.8 Calcium channel blocker verapamil may interfere
with H+K+ ATPase due to its high affinity for the K+
site H+K+ATPase system which is accessible
from luminal side of the stomach.9 Histamine release from peritoneal
mast cells is critically dependent upon extracellular Ca++concentration,
so non-availability of Ca++may cause reduced effects of histamine on
acid production in the stomach. Calcium channel blockers have been mainly used
in CVS as inhibitors of muscle contraction. In the stomach, motility and acid
secretion have been shown to be dependent upon calcium ions. So this study was
planned to evaluate the effects of extract from Myristica fragrans and calcium
channel blocker Verapamil on the volume and acidity of Carbachol induced
gastric secretion. Their effects were also compared on these parameters.
MATERIAL
AND METHODS
Thirty rabbits of local
breed were selected for the present study. Healthy animals of both sexes
weighing 1-1.5kg were used in the study. All the animals were kept fasting for
48 hours with free availability of water before they were subjected to
experimental procedure. The animals were divided into 3 groups each containing
10 animals. Group A was carbachol treated, Group B was Verapamil+ carbachol
treated and Group C. was Myristica fragrans + carbachol treated.
The operative
procedure was the one adopted by Vischer et al.10 Animals were
anaesthetized with ether, abdomen was opened and pylorus was ligated with silk
suture. Then abdominal wall was closed with suture clips and intraperitoneal
(IP) injection of Carbachol 600µg/Kg body weight was administered to group A,
10mg/Kg body weight of Verapamil to group B and 500 mg/Kg body weight of
Myristica fragrans to group C, followed by Carbachol 600µg/Kg body weight after
15 minutes to group B and C. The rabbits were deprived of water for four hours
after administration of drugs. Then the rabbits were sacrificed, the thorax and
abdomen were opened, oesophagus was ligated and the stomach was removed
quickly. The contents of the stomach were collected. The volume of gastric
juice was measured. Then the contents were centrifuged, filtered and subjected
to titration for estimation of free and total acidity by the method described
by Varley.11 One ml of centrifuged and filtered gastric secretion
was titrated against 0.1 N NaOH using Topfers reagent for determination of free
acidty and 1% phenoplphthalein as indicator for combined acidity. The sum of
the two titrations was total acidity. The data was analyzed statistically using
student’s “t” test.
RESULTS
The volume, free acidity and total acidity
of gastric secretion for all the three groups are shown in table-1. The reductions
in groups given verapamil or Myristica Fragrans noticed for all the parameters
were found to be highly significant when compared with Carbachol (P<0.001). When
we compared the mean values of volume, free and total acidity for Verapamil and
extract it was observed that these differences in all the three parameters
between two groups were found to be non significant. All these changes are
shown in Table-2.
DISCUSSION
Acid secretion in the
stomach is controlled at a variety of levels by neural, hormonal and paracrine
mechanisms. When these regulatory mechanisms malfunction acid and pepsin
autodigest the mucosa resulting in the ulceration of oesophagus, stomach and
duodenum.12
Histamine,
acetylcholine or Carbachol are potent secretogogues for the parictal cels of
gastric mucosa leading to the production of HCl.11
Acetylcholine
and gastrin act through calcium ions. Carbachol being a cholinomimetic drug
increases free intracellular calcium ions. Which, in turn activate protein
kinase by phosphorylation and lead to increased production of HCl. In this
study we observed that Myristica fragrans reduced the volume free acidity and
total acidity. This is due to the calcium channel blocking activity of natural
calcium channel blocker present in the extract. All these reductions were
statistically highly significant when compared with the mean values in
Carbachol treated group.
Similar
reduction were observed using Verapamil. All these reductions were found to be
statistically highly significant when compared with Carbachol alone. Our study
is consistent with other workers who concluded that Verapamil significantly
reduces gastric acid secretion.14,15. It is due to the fact that
Verapamil, a well known calcium channel blocker inhibits the calcium influx,
which may be responsible for the observed reductions in volume and acidity of gastric
secretion. Beside this, Verapamil inhibits lipoxygenase pathway during
metabolism of arachidonic acid. So leukotriene, the injurous substance is not
formed and all the arachidonic acid is metabolized through cyclooxygenase
pathway. This will lead to the production of prostaglandin which couples with
Gi protein and inhibits adenyl cyclase and thus decrease HCl production16
Release
of histamine from mast cells is critically dependent on external calcium ions,
so Verapamil by blocking calcium ions can block histamine release which is a
potent agent for HCl secretion.17
When we compared the differences in the mean values
of volume, free acidity and total acidity by Myristica fragrans and Verapamil,
they were all found non significant. This indicates that extract is almost as
effective as Verapamil in decreasing volume, free and total acidity of gastric
secretion. Verapamil is also used in controlling contraction of cardiovascular
smooth muscles18, allergic reaction19 and prevention of
premature labor.20
All of these actions are due to the calcium
channels blocking activity.
CONCLUSION
It is concluded that the
extract of Myristica Fragrans has effects similar to Verapamil and therefore may
be beneficially used as a single drug therapy in patients having peptic ulcer
concurrent with angina, myocardial infarction, prevention of premature labor or
bronchial asthma. Further studies in this regard for evaluation of these
effects are suggested in human subjects.
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