Inhibitory effects of ascaris suum extract On gastric acid secretion in rats

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R.N.P. Nwankwoala
Department of Pharmacology, College of Health Sciences
University of Port Harcourt

Address:
Choba, Port Harcourt,
Rivers State
Nigeria

O.A. Georgewill
Department of Pharmacology, College of Health Sciences
University of Port Harcourt

Address:
Choba, Port Harcourt,
Rivers State
Nigeria

U.O. Georgewill
Department of Pharmacology, College of Health Sciences
University of Port Harcourt

Address:
Choba, Port Harcourt,
Rivers State
Nigeria

Citation: R. Nwankwoala, O. Georgewill & U. Georgewill : Inhibitory effects of ascaris suum extract On gastric acid secretion in rats. The Internet Journal of Pharmacology. 2009 Volume 7 Number 1

Keywords: A Suum extract | inhibition | gastric acid secretion | peptic ulceration

Abstract

The effects of Ascar’s Suum (A. Suum) extract on gastric acid secretion were investigated in urethane-anaesthetised rats. Three determinations were done viz (1) the acid content when no drug was administered (2) the acid content when histamine was injected and (3) the acid content when the A. Suum extract was given alone or after histamine was administered. The extract (5.5 or 14mg/kg) reduced histamine-induced gastric acid secretion to the control value. At 14mg/kg the extract also reduced basal gastric acid secretion. At the peak of histamine-induced gastric acid secretion, the administration of the extract promptly reduced the gastric acid secretion to basal values. These results indicate that extracts of Ascaris Suum inhibit gastric acid secretion.

Introduction

Ascaris Summ is a common parasitic worm found in the small intestine of pigs. Its equivalent in man is Ascaris Lumbricoides (Sprent et al., 1975). Two important findings have been reported about the physiology of Ascaris species: Hogberg et al (1959), using perfused cat paw reported that the extracts of Ascaris Suum caused liberation of histamine. Further, Mellanby (1955) reported that acetylcholine (Ach) was a major constituent of Ascaris Suum. It is now generally accepted that histamine and acetylcholine are perhaps the most important substances that condition and determine the level of acid secreted in the mammalian gut and therefore are implicated in the etiology of peptic ulcers (Card and Monk, 1960; Richardson, 1978; Chierichetti et al., 1979; Texter and Reilly, 1982). It is this fact that informed us to think that the extracts of Ascaris Suum may have effect in modulating acid secretion of its host and hence this investigation.

Materials and method

Animals: Randomly selected young (5-10 weeks old) Albino rats of both sexes weighing 150g- 200g were used. The animals were obtained from the animal house of University of Port Harcourt and kept in the departmental animal house at least 7 days before use. They were fed on chicken mash (Superfeeds Nigeria Ltd., Port Harcourt) and were given drinking water ad libitum. They were starved of food twenty four hours preceeding the experiments.

Drugs and Reagents

Histamine (acid phosphate), phenolphthalcin indictor, urethane and trichloroacetic acid were obtained from Sigma Chemicals U.K.

A Suum Extracts: The worms of Ascaris Suum were collected from the Port Harcourt abattoir, washed with normal saline, and ground with a little amount of fine sand and normal saline solution. Thereafter the resultant solution was centrifuged at 3,000 RPM for 15 minutes. The supernatant was collected. The protein in the supernatant was precipitated with 10% trichloroacetic acid and the mixture was centrifuged at 5,000 RPM for 20 minutes. The resultant supernatant was discarded.

The protein precipitate was redissolved in the saline. This mixture was dialyzed for 24 hours in distilled water in order to remove sodium chloride and trichloroacetic acid. The dialyzed material was then freeze-dried. The resulting freeze-dried substance was stored for use and this was the Ascaris Suum Extract.

Measurement of Gastric Acid Secretion

Each animal was anaesthesized with 25% Urethane (0.6 m1/10g body weight). Subsequently, a tracheostomy was performed and a canula inserted into the trachea and ligated to ensure adequate respiration. Another canula was inserted into the oesophagus through the mouth and ligated. This canula is continuous with a drip set tube which runs from the reservoir bottle containing saline which is placed in the water-bath set at 37 ⁰ C. Thereafter duodenostomy was performed near the gastroduodenal junction and another canula inserted into the stomach through the pyloric end and ligated. The stomach was washed of the food particles. The effluent was collected through the canula inserted into the stomach at the rate of about 9 to 15 mls every 20 minutes. Nothing the volume of effluent, each collection was volumetrically titrated against 0.0025M sodium hydroxide. Two or 3 drops of phenolphthalein was used as the indicator. The volume of the base used to neutralize the acid was recorded, from which the amount of acid in a given effluent was quantitated. Basal secretion effluents were usually collected before the injection of the drugs.

Four (4) types of experiments were carried out: (1) Basal Secretion and Histamine-stimulated gastric acid secretion, (2) Histamine-stimulated gastric acid secretion in the presence and absence of the extract, the effect of the extract on basal secretion, (3) the interception of Histamine-stimulated gastric acid secretion at Peak by the administration of the two doses of the extract used and (4) the effect of the co-administration of the extract and histamine on gastric acid secretion. For each experiment, basal secretion effluents were collected and this was repeated in five animals. In the other experiments, 20mg/kg, histamine was administered intramuscularly Ascaris Suum extract was given as a single bolus-intramuscular injection. These experiments were repeated five times. The mean acid output as calculated. Data is presented as mean and standard deviation from the mean. Where indicated, student’s t-test was used to test for statistical significance. A P value of <0.05 was considered statistically significant.

Results

As shown in Fig 1, histamine at the dose of 30mg/kg produced 70% gastric acid secretion above the basal values. This histamine-induced acid secretion peaked at 2½ hours and remained high at 4½ when the experiment was terminated. Co-administration of 20m1/kg histamine and 14mg/kg Ascaris Suum extract reduced the histamine-induced acid secretions significantly (p<0.001) by 71.5% after 2 hours and thereafter reduced the gastric acid secretion to the basal secretion values (Fig. 2). Administration of the Ascaris extract alone brought the acid secretion to the basal or below basal values.

As illustrated in Fig. 3, when the Ascaris suum extract was administered at the peak of Histamine-induced gastric acid secretion 21/3 hours following series of histamine administration, the two doses of the extract used (5mg/kg an 14mg/kg) reduced the gastric acid secretion to the basal values. This result was also obtained when the extract was co-administered with histamine right from the onset of the experiment as shown in Fig. 4 For example, there was no significant difference (p>0.05) in gastric secretion between the basal value and that obtained when Histamine was co-administered with the ascaris extract whereas histamine administered alone significantly (p<0.001) increased gastric acid secretion.

Discussion

It has been demonstrated that the extracts of Ascaris Suum caused the release of histamine from perfused cat paw (Hogberg et al 1959). It was therefore expected that this extract would increase gastric acid secretion and potentiate histamine-induced gastric acid secretion. On the contrary, the results of this study provide the evidence acid secretion and abolishes histamine-induced gastric acid secretion. The mechanism of Ascaris extract-induced inhibition of gastric acid secretion was not elucidated. However, from the results of this study, it is safe to suggest that the worm extract might contain yet unidentified inhibitors of gastric acid secretion which in turn act (a) directly on parietal cells of gastric mucosa and/or (b) indirectly by causing a release of endogenous inhibitors of gastric acid secretion such as prostaglandins E₂ and 1₂ (Ippoliti et al., 1981).

Figure 1: Basal Acid Secretion and Effect of Histamine on Gastric Acid Secretion. Data represents mean and standard deviation (n=5).

Figure 2: Effect of extract of Ascaris Suum (14mg/kg) on gastric acid secretion either in the presence or absence of 20mg/kg histamine (n=5)

Figure 3: Effect of different doses of Ascaris extract on histamine-induced peak gastric acid secretion (n=5)

Figure 4: Effect of co-administration of Ascaris extract and histamine on gastric acid secretion (n=5).

In this study, the two doses used viz 5.5mg/kg and 14mg/kg Ascaris Suum extract were equipotent in reducing the histamine-induced peak gastric acid secretion to basal secretion values. Although, it is early to conclude from this result that the extract caused inhibition of gastric acid secretion, it is not dose-dependent.

These data suggest that the extract may produce its inhibitory effect on gastric acid secretion by altering the histamine and cholinergic receptor configurations on the partietal cells and not by H₂ receptor blockade.

This view is supported by earlier finding in our laboratory that the Ascaris extract also inhibited carbachol-induced gastric acid secretion (Ezeamuzie and Nwankwoala – unpublished data). It is also possible that at much lower concentrations of the extract e.g microgram or less, dose dependent inhibitory response may be observed. This possibility is currently undergoing investigation in our laboratory.

Ascaris Suum which is hosted by intestinal lumen of pig is morphologically equivalent to Ascaris Lumbricoides which is hosted by intestinal lumen of man. It is possible that these worms may release gastric acid inhibitory proteins or substances which then inhibit gastric acid secretion in the host. The anti-secretory effect of this Ascaris extract may therefore be of potential value in the treatment of peptic ulceration in man. This speculation is in accordance with the finding that patients infested with Ascaris lumbricoides showed a reduced incidence of peptic ulcers 9Konturk, 1983).

References

Card, W.I. and Marks, I.N. (1960): The relationship between the acid output of the stomach following maximal histamine stimulation and the parietal cell mass. Clin Sc. 19 147-157. (s)

Chierichetti, S.M. Gaetanini, M. and Petrini, G. (1979): Pharmakokinetic and Clinical Studies on Pirenzeoine, new antiulcer drug. Scand, J. Gastroentrol, 14 (Suppl. 47) 1-67. (s)

Hogberg, B., Thufvesson, G., and Uvnas, B. (1959): Histamine liberation produced in t he perfused paw of the cat by 48/80 and extracts from jelly fish (Cyanea Capillata) and Eelworm (Ascaris lumbricoides) from Swine .J. Parasitology 25 (3) 1048-1052. (s)

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Konturek, S.J. (1983): Pharmacological control of gastric acid secretion in peptic ulcer. Mt. Sinai J. Med. 50 457-467. (s)

Mcllanby, H. (1955): Identification and estimation of acetylcholine in three parasitic nematodes (Ascaris lumbricoides, litomosoides Carini and the microfilariae of firofilaria repens) Parasitology 45 287-295. (s)

Richardson, C.T.P. (1978): Effect of H2-receptor antagonists on gastric acid secretion and serum gastrin concentration. Gastroenterology 74 366-370. (s)

Sprent, T.F.A. Pearson, J.C., Pawson, D.L. and Ryland in Text Book of Zoology. Invertebrate. Marshal A.J. and Williams, W.D. (eds). 7 th Ed. London Macmillan pp. 235-255. (s)

Texter, E.C. Jr. and Reilly P.A. 91982): The efficacy and selectivity of pirenephine: review and commentary. Scand. Journal of Gastroenterology (Suppl) 72 237-246. (s)

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