Effect of Estrogen on Basal, Charbacol Stimulated Acid Secretion and Indomethacin...

Med. J. Cairo Univ., Vol. 80, No. 1, September: 533-544, 2012

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Effect of Estrogen on Basal, Charbacol Stimulated Acid Secretion and Indomethacin Induced Ulcer in Female Albino Rats

NASHWA M.S. EL-TABLAWY, M.D.; MOHAMED M. OMRAN, M.D.*; AKEF A. KHOWAILED, M.D. and EMAD EL-DIN M.A. TANTAWY, M.Sc.

The Department of Physiology, Faculty of Medicine, Cairo and MUST* Universities

Abstract

Introduction : Peptic ulcer occurs more frequently in men

than in women, sex differences are less marked after 45 years

of age probably because the incidence of ulcer increases in

post menopausal women. The general assumption is that the ulcer differences between sexes are related in some way to

sex hormones and that the female sex hormones protect against

ulceration.

The aim of the this study was to investigate in rats the

effect of ovariectomy on gastric acid secretion and gastric

ulcer and to demonstrate the effect of estrogen, a selective

alpha estrogen receptor agonist 1, 3, 5-tris (4-hydroxyphenyl)- 4-propyl-1H-pyrazol (PPT) and a selective beta estrogen

receptor agonist 2, 3-bis (4-Hydroxyphenyl) Propionitrile

(DPN) on gastric acid secretion on basal, charbacol stimulated

acid secretion and also its effect on indomethacin induced ulcer in ovariectomized rats.

Material and Methods : A total of 90 female albino rats weighing 150-200gm were included in the study. The animals were divided into five groups 18 rats each.

• Group I: The control group.

• Group II: Was subjected to ovariectomy.

• Group III: Was subjected to ovariectomy and estrogen

replacement therapy at a dose of 10µg/rat/day for ten

days.

• Group IV: Was subjected to ovariectomy and a selective

alpha estrogen receptor agonist 1, 3, 5-tris (4- hydroxyphenyl)-4-propyl-1H-pyrazol (PPT) replacement

therapy at a dose of 10µg/rat/day for ten days.

• Group V: Was subjected to ovariectomy and a selective beta

estrogen receptor agonist 2, 3-bis (4-Hydroxyphenyl) Propionitrile (DPN) replacement therapy at a dose of

10µg/rat/day for ten days. Each group is subdivided into

three sub groups formed of 6 rats each.

Subgroup A: In which basal gastric acid secretion was measured and number of ulcers was counted.

Correspondence to: Dr. Nashwa M.S. El-Tablawy, The Department of Physiology, Faculty of Medicine,

Cairo University

Subgroup B: In which gastric acid was induced by Car-bamylcholine chloride (carbachol) 30µg/kg S.C. after three

hours the stomach was removed, acid secretion was measured

and number of ulcers was counted.

Subgroup C: Was subjected to indomethacin induced ulcer by oral administration of indomethacin 48mg/kg after three

hours the stomach was removed, acid secretion was measured

and number of ulcers were counted.

Results : Results showed that gastric acid secretion and

number of ulcers were significantly higher among ovariecto-mized group than in control group when estimated within the

basal acid secretion, carbachol induced acid secretion and

indomethacin induced ulcer sub groups (p<0.05).

There was statistical significant increase in gastric acid

secretion in the ovariectomized with estrogen replacement

group as compared to the control group in basal acid secretion

sub-group only (p<0.05). Also there was statistical significant increase in the number of ulcers in the ovariectomized with

estrogen replacement sub-groups as compared to the control

group (p<0.05), except for indomethacin induced ulcer sub group.

No significant difference had been observed between

ovariectomized with alpha estrogen receptor agonist (PPT) sub-groups and the control group as regard acid secretion and

number of ulcers (p 0.05).

Gastric acid secretion and number of ulcers were signif-icantly higher among ovariectomized with beta estrogen

receptor agonist (DPN) group than in control group in basal

acid secretion and carbachol induced acid secretion sub groups

(p<0.05). While in indomethacine induced ulcer sub group the difference was not significant.

Also the results showed that gastric acid secretion and

the number of ulcers were significantly lower among ovariec-tomized with estrogen replacement group and ovariectomized

with alpha estrogen receptor agonist group compared with

ovariectomized group in all studied sub groups (p<0.05).

The number of ulcers was significantly lower among

ovariectomized with beta estrogen receptor agonist group

than ovariectomized group in all studied sub groups (p<0.05). While Gastric acid secretion was significantly lower among

ovariectomized with beta estrogen receptor agonist group

533

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534 Effect of Estrogen on Basal, Charbacol Stimulated Acid Secretion

compared with ovariectomized group in indomethacine induced ulcer sub group only (p<0.05).

There was no statistical significant difference between ovariectomized with estrogen replacement group compared

with ovariectomized with alpha estrogen receptor agonist group and ovariectomized with beta estrogen receptor agonist

group as regard acid secretion and number of ulcers. Except

there was a significant lower number of ulcers in ovariecto-mized with alpha estrogen receptor agonist group as compared to ovariectomized with estrogen replacement group in the

basal acid secretion and carbachol induced acid secretion sub-groups (p<0.05).

Conclusion : Our data indicate that estrogen decreases

gastric acid secretion and number of peptic ulcers and this

effect occur through stimulation of alpha and beta estrogen

receptors.

This may provide an initial rationale for a potential hormone (estrogen) therapy to protect the GIT in postmeno-pausal women. Hence it is recommended to use estrogen

replacement therapy in postmenopausal women to protect

against gastric and duodenal ulcers.

Key Words: Overictomy – Peptic ulcer – Gastric acid secretion – PPT – DPN.

Introduction

ORIGINALLY identified as reproductive hor-mones, estrogens are now generally thought to play an important roles in bone, cardiovascular,

gastrointestinal and in the central nervous system. This expanded view of estrogen action reflects the

findings of a large number of clinical studies and

huge body of empirical observational data gathered

on the effect of exogenous estrogen administration

on the health of menopausal women. Parallel stud-ies reporting the distribution of estrogen receptors

and others describing specific estrogenic responses in functionally related tissues have led to an appre-ciation of the sphere of influence of this hormone

[1] .

Astric ulcer is a mucosal erosion of stomach,

due to multiple causes, including bacteria Helico-bacter pylori [2] , tobacco smoking, not eating properly, chewing gum, blood group, spice, chronic stress [3] and gender differences [2] . The develop-ment of gastric ulcerations is linked to the changes that occur within hormonal cycles, especially those related to the sex hormones secretion. It is accepted

that the incidence of gastric peptic ulcers increases

among women in menopause [4] . The general as-sumption is that the ulcer differences between sexes are related in some way to sex hormones and that the female sex hormones protect against

ulceration [5] .

Numerous studies have suggested a protective

role of estrogen in the development of various

diseases including cardiovascular diseases [6] ,

cerebral damage and mortality [7] and osteoporosis [8] . Also gender specific protection of estrogen against gastric acid induced duodenal injury by

stimulation of duodenal mucosal bicarbonate se-cretion was reported [9] .

The present study was undertaken therefore, to

investigate in rats the effect of ovariectomy on

gastric acid secretion and gastric ulcer and to

demonstrate the effect of estrogen, a selective alpha

estrogen receptor agonist 1,3,5-tris (4–hydroxyphe-nyl)-4-propyl-1H-pyrazol (PPT) and a selective

beta estrogen receptor agonist 2, 3-bis (4–Hydrox-yphenyl) Propionitrile (DPN) on gastric acid se-cretion on basal, charbacol stimulated acid secretion

and also its effect on indomethacin induced ulcer

in ovariectomized rats.

Material and Methods

Chemicals : • 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-

pyrazole (PPT) a selective estrogen alpha agonist was obtained from Sigma (St. Louis, MO, USA).

• Carbamylcholine chloride (carbachol) was ob-tained from Sigma (St. Louis, MO, USA).

• Dimethyl sulfoxide (DMSO) was obtained from Sigma (St. Louis, MO, USA).

• Indomethacin was obtained from Fluka.

• 2,3-bis (4-Hydroxyphenyl) Propionitrile (DPN) a selective estrogen receptor beta agonist was

obtained from Spi Bio France.

Animals : A total of 90 female albino rats weighing 150-

200gm were housed in wire mesh cages at room temperature, veterinary care was provided by lab-oratory animal house unit of faculty of medicine,

Cairo University (During December 2009). Rats

were housed with normal light and dark cycle and

were allowed to acclimatize to their environment

for five days before start of the experiment. All animal were kept under the same environmental

conditions and had free access to food and water.

The animals were divided into five groups 18 rats each.

Group I: The control group was subjected to sham operation.

Group II: Was subjected to ovariectomy.

Group III: Was subjected to ovariectomy and es-trogen replacement therapy at a dose of

10µg/rat/day for ten days [10] .

Group IV: Was subjected to ovariectomy and a

selective alpha estrogen receptor agonist 1, 3,

Nashwa M.S. El-Tablawy, et al. 535

5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazol (PPT) replacement therapy at a dose of

10µg/rat/day for ten days.

Group V: Was subjected to ovariectomy and a

selective beta estrogen receptor agonist 2, 3- bis (4-Hydroxyphenyl) Propionitrile (DPN) replacement therapy at a dose of 10µg/rat/day

for ten days.

All animals were left for ten days to recover.

Each group is subdivided into three sub groups

formed of 6 rats each.

Subgroup A: In which basal gastric acid secretion

was measured and number of ulcers was count-ed.

Subgroup B: In which gastric acid was induced by

Carbamylcholine chloride (carbachol) 30µg/kg

S.C. after three hours the stomach was re-moved, acid secretion was measured and num-ber of ulcers was counted [11] .

Subgroup C: Was subjected to indomethacin in-duced ulcer by oral administration of in-domethacin 48mg/kg after three hours the

stomach was removed, acid secretion was

measured and number of ulcer was counted

[12] .

Procedures:

- Ovariectomy : An aseptic surgical procedure was employed

for all animals. The rats were anesthetized using ketamine (100mg/kg, IM), then the dorsal part of the lumbar region was shaved, and the site cleaned with 75% ethanol followed by thorough scrubbing

with 10% povidone iodine. A 2cm incision was made in the skin through the musculature and

peritoneum and the ovaries were retracted and

removed. The wound was then closed using a 4- O sterile suture. Immediately after surgery the

wound again cleaned with povidone iodine to

reduce the chance of post-operative infection [13] .

- Sham operation : The animals were subjected to the same steps

in the previous procedure but without removal of

the ovaries.

- Gastric acid measurement: The Stomach was removed and the contents

were drained into a graduated centrifuge tube after

making a small nick along the greater curvature

adjacent to pyloric ligation. The tubes were centri-fuged at 3000 r.p.m. for 10minutes and the centri-fuged samples were decanted and analyzed for

volume, pH (using digital pH meter type DPH-100 USA instruments) and total acidity was measured

by titrating 0.1ml of gastric juice with 0.01 N sodium hydroxide to pH 7 using phenolphthalein

as indicator. Acidity was expressed in clinical units

i.e., the number of milliliters of N/10NaOH base

required to titrate 100ml of gastric secretion [14] .

- Measurement of ulcer :

The number of ulcers in the gastric mucosa was

calculated by using magnifying lens.

Statistical methods :

Data were coded and entered using the statistical

package SPSS version 15. Data was summarized using mean, standered deviation and range for the

quantitative variable. Comparisons between groups

were done using analysis of variance (ANOVA) with multiple comparisons post hoc test in normally

distributed quantitative variables while non para metrical kruscal-wallis test and mann-whitney test

were used for non normally distributed quantitative

variables. correlation were done to test for linear

relations between quantitative variables. p-values less than or equal to 0.05 were considered as

statistically significant.

Results

Table (1), Fig. (1-A,B) show that gastric acid secretion and number of ulcers were significantly

higher among ovariectomized group than in control

group when estimated within the basal acid secre-tion, carbachol induced acid secretion and in-domethacin induced ulcer sub groups (p<0.05).

There was statistical significant increase in

gastric acid secretion in the ovariectomized with

estrogen replacement group as compared to the

control group in basal acid secretion sub-group

only (p<0.05). Also there was statistical significant increase in the number of ulcers in the ovariecto-mized with estrogen replacement sub-groups as

compared to the control group (p<0.05), except for indomethacin induced ulcer sub group Table (2), Fig. (2-A,B).

Table (3), Fig. (3-A,B) show no significant

difference between ovariectomized with alpha

estrogen receptor agonist (PPT) sub-groups and

the control group as regard acid secretion and

number of ulcers (p>0.05). Except the number of ulcers was significantly higher in ovariectomized with alpha estrogen receptor agonist group than in control group only in basal acid secretion sub group

(p-Value <0.05) (Fig. 3-B).

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Groups Control Overiectomized

*

*

* Groups

Control Overiectomized

*

*

*


Gastric acid secretion and number of ulcers

were significantly higher among ovariectomized

with beta estrogen receptor agonist (DPN) group

than in control group in basal acid secretion and

carbachol induced acid secretion sub groups

(p<0.05). While in indomethacine induced ulcer

sub group the difference was not significant Table

(4), Fig. (4-A,B).

Also the results in Tables (5,6), Figs. (5-A,B, 6-A,B) and (5,6-B) showed that gastric acid secre-tion and the number of ulcers were significantly

lower among ovariectomized with estrogen replace-ment group and ovariectomized with alpha estrogen

receptor agonist group compared with ovariecto-mized group in all studied sub groups (p<0.05).

The number of ulcers was significantly lower among ovariectomized with beta estrogen receptor agonist group than ovariectomized group in all

studied sub groups (p<0.05). While Gastric acid secretion was significantly lower among ovariec-tomized with beta estrogen receptor agonist group compared with ovariectomized group in indometha-cine induced ulcer sub group only ( p<0.05) Table (7), Fig. (7-A,B).

There was no statistical significant difference

between ovariectomized with estrogen replacement

group compared with ovariectomized with alpha

estrogen receptor agonist group and ovariectomized

with beta estrogen receptor agonist group as regard acid secretion and number of ulcers Tables (8,9),

Fig. (8-A,B, 9-A,B). Except there was a significant

lower number of ulcers in ovariectomized with alpha estrogen receptor agonist group as compared

to ovariectomized with estrogen replacement group

in the basal acid secretion and carbachol induced

acid secretion sub-groups (p<0.05) Fig. (8).

Table (1): Comparison between control group and ovariectomized group in terms of gastric acid secretion and number of ulcers

in different studied sub-groups.

Control Ovariectomized (OVX) p-value

Mean ± SD Mean ± SD

Basal acid secretion Gastric acid secretion (mmol/L) 3.3567±.68313 4.5167±.31513 .002* Number of ulcers 0.000 5.8333±1.16905 .002*

Carbachol induced acid secretion Gastric acid secretion 3.9650±.16009 5.0350±.46120 .002* Number of ulcers 2.6667±.81650 6.8333±1.16905 .002*

Indomethacin induced ulcer Gastric acid secretion 4.3567±.37877 5.7250±.50508 .004* Number of ulcers 4.0000±.89443 7.8333±1.16905 .002*

*Means significant (p-value <0.05).

Basal Carbachol Indometh Basal Carbachol Indometh induced induced induced induced

Subgroups Subgroups

Fig. (1-A): Comparison between control group and ovariec-tomized group in terms of gastric acid secretion

(mmol/L) in different studied sub-groups.

Fig. (1-B): Comparison between control group and ovariec-tomized group in terms of number of ulcers in

different studied sub-groups.

Basal Carbachol Indometh induced induced

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*


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Groups Control OVX+Estrogen replacement

* *


Table (2): Comparison between control group and ovariectomized with estrogen replacement group in terms of gastric acid

secretion and number of ulcers in different studied sub-groups.

Control OVX+Estrogen replacement p-value


Basal acid secretion

Carbachol induced acid secretion

Indomethacin induced ulcer

Gastric acid secretion (mmol/L) Number of ulcers

Gastric acid secretion Number of ulcers


3.3567±.68313 0.000

3.9650±.16009 2.6667±.81650

4.3567±.37877 4.0000±.89443

4.0750±.28613 4.1667± 1.60208

4.1917±.32823 4.8333±.75277

4.3767±.37066 4.5000±1.87083

.015 *

.002 *

.180

.004 *

.937

.699


Subgroups

Fig. (2-A): Comparison between control group and ovariec-tomized with estrogen replacement group in terms of gastric acid secretion (mmol/L) in different

studied sub-groups.

Subgroups

Fig. (2-B): Comparison between control group and ovariec-tomized with estrogen replacement group in terms

of number of ulcers in different studied sub-groups.

Table (3): Comparison between control group and ovariectomized with alpha estrogen receptor agonist (PPT*) group in terms

of gastric acid secretion and number of ulcers in different studied sub-groups.

Control OVX+Alpha

estrogen agonist p-value Mean ± SD Mean ± SD







3.3567±.68313 0.000

3.9650±.16009 2.6667±.81650

4.3567±.37877 4.0000±.89443

3.9633±.42017 2.1667±.98319

4.2650±.46933 3.1667±.98319

4.4233±.45355 4.6667±.51640

.093

.002*

.240

.394

.485

.240

*PPT = 1, 3, 5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole.



Basal Carbachol induced

Indometh induced


Indometh induced


Indometh induced


Indometh induced

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Groups Control OVX+Alpha estrogen agonist

Subgroups

Fig. (3-A): Comparison between control group and ovariec-tomized with alpha estrogen receptor agonist (PPT)

group in terms of gastric acid secretion (mmol/L)


Num

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Groups Control OVX+Alpha estrogen agonist

*

Subgroups

Fig. (3-B): Comparison between control group and ovariec-tomized with alpha estrogen receptor agonist (PPT)

group in terms of number of ulcers in different studied sub-groups. (Fig. 3-B).

Table (4): Comparison between control group and ovariectomized with beta estrogen receptor agonist (DPN*) group in terms

of gastric acid secretion and number of ulcers in different studied sub-groups.

Control OVX + Beta estrogen agonist p-value

Mean±SD Mean±SD

Basal acid secretion Gastric acid secretion (mmol/L) 3.3567±.68313 4.0850±.62356 .041* Number of ulcers 0.000 2.6667±.51640 .002*

Carbachol induced acid secretion Gastric acid secretion Number of ulcers

3.9650±.16009 2.6667±.81650

4.6117±.54396 5.0000±.89443

.015*

.004*

Indomethacin induced ulcer Gastric acid secretion 4.3567±.37877 4.5117±.40415 .485 Number of ulcers 4.0000±.89443 5.5000±1.51658 .093

*DPN = 2, 3-bis (4-Hydroxyphenyl) Propionitrile. *Means significant (p-value <0.05.

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6.500

3.250

0.000

1.625

Groups Control OVX+Beta estrogen agonist

* *

Subgroups

Fig. (4-A): Comparison between control group and ovariec-tomized with beta estrogen receptor agonist (DPN)

group in terms of gastric acid secretion (mmol/L)


Num

ber

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Groups Control OVX+Beta estrogen agonist

*

*

Subgroups

Fig. (4-B): Comparison between control group and ovariec-tomized with beta estrogen receptor agonist (DPN)

group in terms of number of ulcers in different studied sub-groups.


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Groups Overiectomized OVX+Estrogen replacement

* * *


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Groups Overiectomized OVX+Estrogen replacement

* *

Ovareictomized (OVX)

Mean ± SD

OVX + Alpha estrogen agonist

Mean ± SD

p-value


Table (5): Comparison between ovariectomized group and ovariectomized with estrogen replacement group in terms of gastric

acid secretion and number of ulcers in different studied sub-groups.

Control OVX+Estrogen

replacement p-value








4.5167±.31513 5.8333±1.16905

5.0350±.46120 6.8333±1.16905

5.7250±.50508 7.8333±1.16905

4.0750±.28613 4.1667± 1.60208

4.1917±.32823 4.8333±.75277

4.3767±.37066 4.5000± 1.87083

.026*

.093

.009*

.015*

.002*

.009*


Subgroups

Fig. (5-A): Comparison between ovariectomized group and

ovariectomized with estrogen replacement group in terms of gastric acid secretion (mmol/L) in


Subgroups

Fig. (5-B): Comparison between ovariectomized group and

ovariectomized with estrogen replacement group in terms of number of ulcers in different studied sub-groups.

Table (6): Comparison between ovariectomized group and ovariectomized with alpha estrogen receptor agonist (PPT*) group

in terms of gastric acid secretion and number of ulcers in different studied sub-groups.







4.5167±.31513 5.8333±1.16905

5.0350±.46120 6.8333±1.16905

5.7250±.50508 7.8333±1.16905

3.9633±.42017 2.1667±.98319

4.2650±.46933 3.1667±.98319

4.4233±.45355 4.6667±.51640

.026*

.002*

.026*

.002*

.002*

.002*

*PPT = 1, 3, 5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole.


Indometh induced

Indometh induced


Subgroups


Subgroups


Indometh induced


Indometh induced


6.00

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* *

*

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6.00

4.00

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*

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Groups Overiectomized OVX+Alpha Estrogen agonist

Fig (6-A): Comparison between ovariectomized group and

ovariectomized with alpha estrogen receptor ago-nist (PPT) group in terms of gastric acid secretion (mmol/L) in different studied sub-groups.

Fig (6-B): Comparison between ovariectomized group and

ovariectomized with alpha estrogen receptor ago-nist (PPT) group in terms of number of ulcers in


Table (7): Comparison between ovariectomized group and ovariectomized with beta estrogen receptor agonist (DPN*) group

in terms of gastric acid secretion and number of ulcers in different studied sub-groups.

Ovareictomized (OVX)

OVX + Beta estrogen agonist p-value


Basal acid secretion Gastric acid secretion (mmol/L) Number of ulcers

4.5167±.31513 5.8333±1.16905

4.0850±.62356 2.6667±.51640

.180

.002*

Carbachol induced acid secretion Gastric acid secretion 5.0350±.46120 4.6117±.54396 .240 Number of ulcers 6.8333±1.16905 5.0000±.89443 .026*

Indomethacin induced ulcer Gastric acid secretion 5.7250±.50508 4.5117±.40415 .004* Number of ulcers 7.8333±1.16905 5.5000±1.51658 .015*

*Means significant (p-Value <0.05).

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Groups Overiectomized OVX+Beta Estrogen agonist

*

Subgroups

Fig. (7-A): Comparison between ovariectomized group and

ovariectomized with beta estrogen receptor agonist

(DPN) group in terms of gastric acid secretion

(mmol/L) in different studied sub-groups.

Num

ber

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Groups Overiectomized OVX+Beta Estrogen agonist

*

*

*

Subgroups

Fig. (7-B): Comparison between ovariectomized group and

ovariectomized with beta estrogen receptor agonist

(DPN) group in terms of number of ulcers in



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Groups OVX+Estrogen replacement OVX+Alpha Estrogen agonist


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Groups OVX+Estrogen replacement OVX+Alpha Estrogen agonist

*

*


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Groups OVX+Estrogen replacement OVX+Beta Estrogen agonist


Table (8): Comparison between ovariectomized with estrogen replacement group ovariectomized with alpha estrogen receptor

agonist (PPT*) group in terms of gastric acid secretion and number of ulcers in different studied sub-groups.

OVX + Estrogen replacement

OVX + Alpha estrogen agonist p-value








4.0750±.28613 4.1667± 1.60208

4.1917±.32823 4.8333±.75277

4.3767±.37066 4.5000±1.87083

3.9633±.42017 2.1667±.98319

4.2650±.46933 3.1667±.98319

4.4233±.45355 4.6667±.51640

.485

.026*

.937

.015*

.589

.937

*PPT = 1, 3, 5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole. *Means significant (p-Value <0.05).

Subgroups

Fig. (8-A): Comparison between ovariectomized with estrogen

replacement group ovariectomized with alpha es-trogen receptor agonist (PPT) group in terms of

gastric acid secretion (mmol/L) in different studied sub-groups.

Subgroups

Fig. (9-A): Comparison between ovariectomized with estrogen

replacement group and ovariectomized with beta estrogen receptor agonist (DPN) group in terms of gastric acid secretion (mmol/L) in different studied sub-groups.

Subgroups

Fig. (8-B): Comparison between ovariectomized with estrogen replacement group ovariectomized with alpha estrogen receptor agonist (PPT) group in terms

of number of ulcers in different studied sub-groups.

Subgroups

Fig. (9-B): Comparison between ovariectomized with estrogen replacement group and ovariectomized with beta

estrogen receptor agonist (DPN) group.


Table (9): Comparison between ovariectomized with estrogen replacement group and ovariectomized with beta estrogen receptor

agonist (DPN*) group in terms of gastric acid secretion and number of ulcers in different studied sub-groups.

OVX+Estrogen replacement

OVX+Beta Estrogen agonist

p-value Mean ± SD Mean ± SD

Gastric acid secretion (mmol/L) 4.0750±.28613 4.0850±.62356 .818 Basal acid secretion

Number of ulcers 4.1667±1.60208 2.6667±.51640 .065

Gastric acid secretion 4.1917±.32823 4.6117±.54396 .180 Carbachol induced acid secretion

Number of ulcers 4.8333±.75277 5.0000±.89443 .818

Indomethacin induced ulcer Gastric acid secretion 4.3767±.37066 4.5117±.40415 .589 Number of ulcers 4.5000±1.87083 5.5000±1.51658 .394

*DPN = 2, 3-bis (4-Hydroxyphenyl) Propionitrile. *Means significant (p-Value <0.05).

Discussion

Gastric mucosal integrity is maintained by many factors, including blood flow, mucus and bicarbon-ate. Prostaglandins (PG)s, in particular, play an important role in the defensive mechanisms [15] . Etradiol replacement significantly reversed OVX-induced decreases in gastric CGRP levels to normal

levels in rats by increasing transcription in DRGs

[16] . Also estrogen has been shown to increase the

production of Calcitonine gene related peptide

(CGRP) in sensory neurons and CGRP plays a critical role in the reduction of stress-induced

gastric mucosal injury by increasing gastric pros-tacyclin (PGI2) levels in rats [17] . In the stomach, prostaglandins stimulate HCO 3

– by affecting the

gastric EP1 receptors [18,19] . Indomethacin exerts its ulcerogenic effect through inhibition of pros-taglandins directly. And also through inhibition of

prostaglandins indirectly by inhibition of NO re-lease [20] .

The basal level of gastric acid output was higher

in ovariectomized (OVX) rats without estradiol-17 beta (EST) than in OVX rats with EST [21] . This report is consistent with our result that showed

significant increase ingastric acid secretion in OVX rats compared to OVX rats treated with estrogen.

Estrogen had been shown to have antiulcer activity and both, progesterone and estrogenes attenuated the area of acute gastric lesions induced

by aspirin and indomethacin [22] .

In addition clinical observations showing that

pregnant women with high estrogen levels of pla-cental origin barely develop ulcers and women

taking oral contraceptives (estrogen/progesterone

compounds) have significantly reduced incidence of ulcers in the stomach [23] .

These previous findings are consistent with our

result that showed the number of ulcers was sig-nificantly lower among OVX rats with estrogen replacement compared with OVX rats in carbachol

induced acid secretion and indomethacin induced

ulcer sub groups. In contrast, it was reported that

17ß-estradiol exerted pro-ulcerogenic influence

by aggravating cysteamine-induced gastroduodenal

ulcers [24] .

Concerning the role of estrogen receptor ago-nists alpha and beta, our results presumably indicate that the effect of estrogen on gastric acid secretion

and gastric ulceration were more pronounced through estrogen receptor alpha agonist than through estrogen receptor beta agonist when com-pared with the control group results. As there is

no significant difference in gastric acid secretion and number of ulcers between OVX with estrogen

receptor alpha agonist (PPT) replacement group

and control group while our results showed that

gastric acid secretion and gastric ulceration were

significantly higher in OVX with estrogen receptor beta agonist (DPN) replacement group than control

group.

In the present study by comparing the results of OVX with estrogen receptor alpha agonist (PPT) replacement group with those of the OVX with

estrogen replacement, it was found that gastric

acid secretion in all sub-groups shows no significant

difference. Moreover number of ulcers was signif-icantly lower among ovariectomized with alpha

estrogen receptor agonist group compared with

ovariectomized with estrogen replacement group

in basal acid secretion and carbachol induced acid

secretion sub-groups. But there was no significant change in indomethacin induced ulcer sub-group.


Also by comparing the results of OVX with estrogen receptor beta agonist (DPN) replacement

group with those of the OVX with estrogen replace-ment group, it was found that there is no statistical

significant difference in gastric acid secretion and

number of ulcers in all sub-groups.

These results confirm that both alpha and beta

estrogen receptor agonists have the same effect as

estrogen on gastric acid secretion and number of ulcers but the effect of alpha estrogen receptor

agonist is more potent than the effect of beta

estrogen receptor agonist. While, it was found that

the alpha and beta estrogen receptor agonists (PPT and DPN) significantly stimulated duodenal mu-cosal bicarbonate secretion with similar efficacies

[9] .

This study revealed that estrogen decreases gastric acid secretion and peptic ulcer and this

effect occur through alpha and beta estrogen re-ceptors and this may provide an initial rationale

for a potential hormone (estrogen) therapy to protect

the GIT in postmenopausal women.

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Effect of Estrogen on Basal, Charbacol Stimulated Acid Secretion and Indomethacin...

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