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Prevention by bismuth subsalicylate of gastric mucosal lesions in response to noxious stimuli in rats
Pharmacological Research Communications, Vol. 10, No. 1, 1978
13
PREVENTION BY BISMUTH SUBSALZCYLATE OP GASTRIC MUCOSAL LESIONS IN RESPONSE TO NOXIOUS STI~JLI IN RATS Marvin M. Goldenberg, LeEoy J. Honkomp, and Alan W. Castellion Section of Pharmacology, Biological S c i e n c e s Division, Norwich Pharmacal Company a n d Eaton Laboratories, Division of Morton-Norwich Produc~, Inc., Norwich, New York 13815 Received in final form 25 November 1977
SUMMARY A series of experiments was conducted to determine the efficacy of bismuth subsalicylate slurry in protecting the rat stomach from hemorrhagic lesion or erosion formation resulting from various noxious stimuli.
Bismuth
subsallcylate slurry (8.75%), at 0.2, 0.6 or 1.0 ml total dose, significantly reduced ulceration of the rat stomach caused by cold + restraint stress (CRS), aspirin and CRS, an ethyl alcohol load, or Tabasco sauce.
The possibility of
a protective coating effect by bismuth subsallcylate slurry was enhanced by finding particles of the compound in a majority of the stomachs examined.
The
mechanism of action of bismuth subsalicylate remains to be elucidated.
INTRODUCTION It was previously reported that preadmlrListered Pepto-Bismol (R)* Liquid was capable of protecting the gastric muoosa of rats against the formation of hemorrhagic lesions in response to cold + restraint stress, and to ethyl alcohol (Goldenberg et al., 1975).
Bismuth subsalicylate is the major in-
gredient in this well-established liquid preparation.
B i s ~ t h salts have
classically been used for treatment in peptic ulcer and their activity has .
.
.
.
.
.
_ .
.
.
.
.
.
.
.
.
.
.
.
*Registered trademark of Morton-Norwich Product~, Inc.
.
_ . . . .
,
_
~
t4
Pharmacological Research Communications, VoL 10, No. 1, 1978
been partially associated with a demulcent-llke protection of the affected mucosa from chemical or mechanical irritation (Harvey, 1970).
The objective
of the present study was to investigate the protective effect of bismuth subsallcylate against hemorrhagic leslon formation in the glandular mucosa of the rat stomach under conditions of stress or potential ulcer-inducing drugs.
Cold + restralnt stress.
Male Sprague-Dawley rats (Charles River
Breeding Laboratories, Inc.), weighing 175-230 g, were fasted for 27 hr before the experiment.
The method used to induce gastric hemorrhagic
lesions by means of 3-hr cold + restraint stress (CRS} was previously described (Golde.nberg, 1973t Goldenberg et el., 1975).
Each stomach was
opened along the limiting ridge and greater curvature to expose the corpus and forestomach regions.
Hemorrhagic lesions of the glandular mucosa were
observed and tabulated. Bismuth subsalicylate slurry (a watery mixture of insoluble bismuth subsallcylate at 8.75%) or distilled water (vehicle control} was administered perorally, at requisite volumes, to rats and 30 rain later rats were subjected to CRS for 3 hr and then killed.
The total doses of bismuth subsalicylate
slurry used were 0.2, 0.6, and 1.0 ml, equivalent to 1.0, 3.0, or 5.0 ml of bismuth subsalicylate in Pepto-Bismol.
The Kruskal-Wallis H test (Brownlee,
1965) for nonparametric statistical analysis of the data was used to determine significance of differences between drug-treated and control groups~ ~ p i r i n and CRs-
Male Wistar-derived rat~ (Charles River Breeding
Laboratories, Inc.), weighing 200-250 g, were fasted for 24 hr before the experiment.
CRS gastric lesions were evoked as described previously (Golden-
berg, 1973; Brownlee, 1965).
Bismuth subsalicylate slurry or distilled water
was administered at doses of 0.2, 0.6, and 1.0 ml 15 rain before the peroral
Pharmacological Research Communications, VoL 10, No. 1, 1978
15
administration of aspirin, 50 mg/kg, which was followed by 3 hr CRS.
After
the rats were killed, the stomachs were examined for hemorrhagic lesions. The mean numbers of leslons in the bismuth subsalicylate slurry and control rat stomachs were compared statistically according to the Kruskal-Wallis H test. Alcohol-induced gastri c !esion~s.
Fe~le
Wistar-derived rats (Carworth
Farms), weighing 200-225 g, were starved for 20 hr prior to use.
Groups of
10 rats each were dosed perorally with bismuth subsalicylate slurry (0.2, 0.6, or 1.0 ml) 10, 30, or 60 rain before peroral administration of 50% ethyl alcohol, 1 or 3 ml.
A vehicle control group was given 1.0 ml of distilled
water i0 min before administered of 1 or 3 ml of 50% ethyl alcohol.
All
animals 'were killed 3-1/2 hr following the dose of ethyl alcohol. Tabasco sauce-induced lesions .. Twenty-one adult male Sprague-Dawley rats, weighing 265-325 g, were fasted 24 hr before the test. were divided into 3 groups of 7 each.
The animals
Group 1 was pretreated with distilled
water (control), 0.2 or 0.6 ml p.o., and t2Le other 2 groups with bismuth subsalicylate slurry, 0.2 and 0~6 ml p.o., respectively.
Ten rain later
each animal was perorally dozen with Tab~Lsco brand pepper sauce (McIlhenny Co., Avsry Island, La.), 1 ml/100 g body weight.
The rats were returned
to their cages (no food or water available) and 3 hr later the animals ~ere killed and the stomachs excised.
RESULTS CRS.
Bismuth subsallcylate slurry, at doses of 0,.2, 0.6, and 1.0 ml,
caused a dose-related inhibition of gastric hemorrhagic formation in response to CRS (Table I).
At the two higher dose-levels bismuth subsalicylate par-
ticles were found in the zumen and gastric mucosa regions of most stomachs examined 3-1/2 hr after dosing.
16
Pharmacological Research Communications, Vol. 10, No. 1, 1978 TABLE I EFFECT OF BISMUTH SUBSALIC~LATE SLURRY IN PREVENTING HEMORRHAGIC IZSIONS OF THE GASTR£C MUCOSA OF THE RAT INDUCED BY 3-HR COLD + RESTRAINT STRESS
Volume ml
Treatment
No. of rats
(+_ S.E.M. ) Mean no. of lesions /stomach
Control (distilled water)
0.2
I0
2.9 + 0.3
Control
0.6
I0
3.3 + 1.1
control
1.0
7
BismUth subsalicylate
0.2
I0
2.3 + 0.5
Bismuth subsalicylate
0.6
13
1.9 + 0.5
Bismuth subsalicylate
1.0
8
4.1+1.5
0.9 + 0.7 a
asignificantly different from control group; p
Aspirin and CRS,
AS shown in Table IX, bismuth subsalicylate slurry,
at 0.2, 0.6, and 1.0 mi, elicited a marked and significant dose-related reduction in the number of hemorrhagic lesions as compared to control.
Bismuth
subsalicylate particles were found in rat stomachs at all dose levels; they were most prevalent at 0.6 and 1.0 ml doses. Alcoh01-induced " gastric lesions.
Bismuth subsalic-llate slurry at 10 =,
30-, or 60-rain pretreatment intervals evoked dose-rela~-d protection of the gastric
mucosae
of rats following 1 or 3 ml of 50% ethyl alcohol (Table XII).
At a given dose of bismuth subsalicylate slurry, pretreatment time interval is inversely related to protection from lesion formation.
Particles of
bismuth subsalicylate were visible in the stomachs of treated rats at all doses and at all pretreatment intervals.
Pharmacclogical Research Communications,, Vol. 10, No. 1, 1978
17
TABLE II EFFECT OF BISLrOTH SUBSALICYLATE SLURRY IN PREVENTING HEMORRHAGIC LESIONS OF %~IE GASTRIC MUCOSA OF THE RAT INDUCED ASPIRIN AND 3-HR COLD + RESTRAINT STRESS
Treatment
Volume ml
NO. of rats
(t S.E.~. ) Mean no. of lesions /stomach
Control (distilled water)
0.2
8
9.0+1.5
Control
0.6
8
9.1 + 1.8
Control
1.0
8
7.0+0.5
Bismuth subsalicylate
0.2
8
3.4 +
Bismuth subsalicylate
0°6
8
2.6 + 0.8 a
Bismuth subsalicylate
1.0
8
2.1 + 0 . 8 a
0.9 a
asignificantly d~fferent from control group; p<0.05.
T abascolsauce-induce d lesions.
Bismuth subsalicylate, 0.2 and 0.6 ml,
caused a dose-related significant reduction in the number of hemorrhagic lesions induced by Tabasco sauce (Table IV).
Capsicum, the irritant subs~tance
derived from pepper, has been demonstrated to cause irritation and hemorrhage in human stomachs (Viranuvatti et al., 1972).
DISCUSSION Previously, Pepto-Bismol liquid was reported to protect the gastric mucosa of rats from hemorrhagic lesion formation in response to CRS, to a combination of aspirin and CRS, and to ethyl alcohol (Goldenberg et al., 1975).
In the present study, bismuth subsalicylate was found to hs the agent
responsible for the degree of protection afforded by Pepto-Bismol liquid.
0.2 0.6 1.0
pretreatment
30 rain pretreatment '
60 ~ n
4.3 + 0.7 b 1.5 ~ 0.7 b 0.9 ~ 0.3 b
3.3 + 1.5 b 0.7 ~ 0.5b 0.0 ~- 0.0 b
1.7 + 0.6 b 0.5 ~ 0.4 b 0.i ~ 0.I b
0.2 0.6 1.0
0.2 0.6 1.0
6.5 + 1.4 a
4.0 ~ i.ib 2.6 ? 0.6b
3.9 + 0.8 b
0.8 ~ 0.2 b
2,1 ~" o.sb
4.9 + 1.0 b
4.6 + 1.0 b 1.6 ~ 0.5 b 1.3 ~ 0.5 b
8.6 + 0.6
3 ml 50% ethyl alcohol Mean no. of lesions/stomach
l~0 rain p r e t r e a t m e n t
~ m! 50% eth~10 alc phol Mean no. of lesions/stomach
1.0
(ml)
Dose
bsi~ificantly different from control group; p<_O.05.
aM.e~n + S.E.M.
Bismuth subsalicylate slurry " "
v!
Bismuth subsalicylate slurry
slurry
Distilled water (control) Bismuth subsaliaylate
Treatment
EFFECT OF BISMU~q SUBSALICYLATE SLURRY ON GASTRIC HEMORRHAGIC LESIONS IN RATS INDUCED BY 50% ETHYL ALCOHOL
TABLE III
co
Pharmacological Research Communications, Vol. 10, No. 1, 1978
19
TABLE IV ACTION OF BISMUTH SUBSALIC~LATE SLURRY ON GASTRIC HEMORRHAGIC LESION FORMATION INDUCED BY TABASCO BRAND PEPPER SAUCE IN RATS
Treatment
Control (distilled water)
Volume ml
0,2-0.6
No. of rats
(+ S.E.Mo) (Mean no. of lesions /stomach
7
6.4 + 1.3
Bismuth subsallcylate
0.2
7
4.6 + 1.2
Bismuth subsalicylate
0.6
7
1 o7 + 0.6 a
asignificantly different from control group; p<0.05.
That is, bismuth subsalicy!ate caused significant dose-related protection of the rat gastric mucosae, regardless of ~at s~rain or sex, against various noxious factors known to lead to erosions or hemorrhagic lesions. Bismuth compounds have been described as forming a protective barrier in the stomach against noxious stimuli (Weiss and Serfontein, 1971).
Weiss
and Serfontein (1971) have proposed that the beneficial effects of a bismuth-protein-complex agent in treating patients with gastric and duodenal ulcers could be due to rapid covering of the ulcer surfaces with a protecting layer of insoluble, bismuth-containing-complex material.
In the present
study, particles of bismuth subsalicylate were found in the stomachs of rats exposed to the stressful situations.
Such findings suggest an interaction
between the bismuth subsalicylate and the factors responsible for lesion format/on, with resulting protection of the gastric mucosal barrier. Aspirin breaks ~ e
gastric mucosal barrier in animals and man (Rainsford,
1975~ Baskin et al., 1976).
Alcohol damages the stomach by sloughing off
the protective superficial mucosal cells, leading to rapid cell death
Pharmacological Research Communications, VoL 10, No. 1, 1978
20 (Rainsford, 1975).
Capsicum causes hemorrhagic lesions through its irritant
effect on the mucosa (Viranuvattl, 1972).
Since cyclic AMP is involved in
the control of cell permeability in the mucosa, the decrease of this nucleotide might be involved in ethanol- or aspirin-induced gastric n~cosal damage (Puurunen and Karppanen, 1975).
The exact mechanism of the protective
effect of bismu~% subsalicylate against these ulcerative factors remains to be elucidated.
Suffice it to say that the gastric mucosal barrier is posi-
tively reinforced by the administration of bismuth subsalicylate to withstand the induction of gastric erosions by a multltude of factors working through different ulcerogenic mechanisms.
REFERENCES Baskin, W.N., Ivey, K.J.~. Krause, W.J., Jeffrey, G.E. and Gemme!i, R.T. (1976). Ann. Int. Med. 85: 299. Brownlee, K.A.
(1965)
°
Statistical Theory and Methodology in Science and
Engineering, 2nd ed., John Wiley & Sons, Inc., New York, p 163-166. Goldenberg, M~M.
(1973). Life Sciences 12: 519.
Goldenberg, M.M., .Honkomp, L.J., Burrous, S.E. and Castellion, A.W.
(1975).
Gastroenterology 69. 636. Harvey, S.C.
(1970'). The Pharmacological Basis of Therapeutics, MacMillan,
New York, p 1002-1019. Puurunen, J. and Karppanen, H. (1975). Rainsford, K.D.
(1975) o
Life Sciences 16: 152:3.
Agents and Actions 5: 326.
Viranuvatti, V., Kalayasiri, C., ChearaniF O. and Plengvanit, V. (1972). Amer. J. Gastroent. 58: 225° Weiss, G. and Serfontein, W.J. (1971).
S. Afr. Med. J. 45: 467.
13
PREVENTION BY BISMUTH SUBSALZCYLATE OP GASTRIC MUCOSAL LESIONS IN RESPONSE TO NOXIOUS STI~JLI IN RATS Marvin M. Goldenberg, LeEoy J. Honkomp, and Alan W. Castellion Section of Pharmacology, Biological S c i e n c e s Division, Norwich Pharmacal Company a n d Eaton Laboratories, Division of Morton-Norwich Produc~, Inc., Norwich, New York 13815 Received in final form 25 November 1977
SUMMARY A series of experiments was conducted to determine the efficacy of bismuth subsalicylate slurry in protecting the rat stomach from hemorrhagic lesion or erosion formation resulting from various noxious stimuli.
Bismuth
subsallcylate slurry (8.75%), at 0.2, 0.6 or 1.0 ml total dose, significantly reduced ulceration of the rat stomach caused by cold + restraint stress (CRS), aspirin and CRS, an ethyl alcohol load, or Tabasco sauce.
The possibility of
a protective coating effect by bismuth subsallcylate slurry was enhanced by finding particles of the compound in a majority of the stomachs examined.
The
mechanism of action of bismuth subsalicylate remains to be elucidated.
INTRODUCTION It was previously reported that preadmlrListered Pepto-Bismol (R)* Liquid was capable of protecting the gastric muoosa of rats against the formation of hemorrhagic lesions in response to cold + restraint stress, and to ethyl alcohol (Goldenberg et al., 1975).
Bismuth subsalicylate is the major in-
gredient in this well-established liquid preparation.
B i s ~ t h salts have
classically been used for treatment in peptic ulcer and their activity has .
.
.
.
.
.
_ .
.
.
.
.
.
.
.
.
.
.
.
*Registered trademark of Morton-Norwich Product~, Inc.
.
_ . . . .
,
_
~
t4
Pharmacological Research Communications, VoL 10, No. 1, 1978
been partially associated with a demulcent-llke protection of the affected mucosa from chemical or mechanical irritation (Harvey, 1970).
The objective
of the present study was to investigate the protective effect of bismuth subsallcylate against hemorrhagic leslon formation in the glandular mucosa of the rat stomach under conditions of stress or potential ulcer-inducing drugs.
Cold + restralnt stress.
Male Sprague-Dawley rats (Charles River
Breeding Laboratories, Inc.), weighing 175-230 g, were fasted for 27 hr before the experiment.
The method used to induce gastric hemorrhagic
lesions by means of 3-hr cold + restraint stress (CRS} was previously described (Golde.nberg, 1973t Goldenberg et el., 1975).
Each stomach was
opened along the limiting ridge and greater curvature to expose the corpus and forestomach regions.
Hemorrhagic lesions of the glandular mucosa were
observed and tabulated. Bismuth subsalicylate slurry (a watery mixture of insoluble bismuth subsallcylate at 8.75%) or distilled water (vehicle control} was administered perorally, at requisite volumes, to rats and 30 rain later rats were subjected to CRS for 3 hr and then killed.
The total doses of bismuth subsalicylate
slurry used were 0.2, 0.6, and 1.0 ml, equivalent to 1.0, 3.0, or 5.0 ml of bismuth subsalicylate in Pepto-Bismol.
The Kruskal-Wallis H test (Brownlee,
1965) for nonparametric statistical analysis of the data was used to determine significance of differences between drug-treated and control groups~ ~ p i r i n and CRs-
Male Wistar-derived rat~ (Charles River Breeding
Laboratories, Inc.), weighing 200-250 g, were fasted for 24 hr before the experiment.
CRS gastric lesions were evoked as described previously (Golden-
berg, 1973; Brownlee, 1965).
Bismuth subsalicylate slurry or distilled water
was administered at doses of 0.2, 0.6, and 1.0 ml 15 rain before the peroral
Pharmacological Research Communications, VoL 10, No. 1, 1978
15
administration of aspirin, 50 mg/kg, which was followed by 3 hr CRS.
After
the rats were killed, the stomachs were examined for hemorrhagic lesions. The mean numbers of leslons in the bismuth subsalicylate slurry and control rat stomachs were compared statistically according to the Kruskal-Wallis H test. Alcohol-induced gastri c !esion~s.
Fe~le
Wistar-derived rats (Carworth
Farms), weighing 200-225 g, were starved for 20 hr prior to use.
Groups of
10 rats each were dosed perorally with bismuth subsalicylate slurry (0.2, 0.6, or 1.0 ml) 10, 30, or 60 rain before peroral administration of 50% ethyl alcohol, 1 or 3 ml.
A vehicle control group was given 1.0 ml of distilled
water i0 min before administered of 1 or 3 ml of 50% ethyl alcohol.
All
animals 'were killed 3-1/2 hr following the dose of ethyl alcohol. Tabasco sauce-induced lesions .. Twenty-one adult male Sprague-Dawley rats, weighing 265-325 g, were fasted 24 hr before the test. were divided into 3 groups of 7 each.
The animals
Group 1 was pretreated with distilled
water (control), 0.2 or 0.6 ml p.o., and t2Le other 2 groups with bismuth subsalicylate slurry, 0.2 and 0~6 ml p.o., respectively.
Ten rain later
each animal was perorally dozen with Tab~Lsco brand pepper sauce (McIlhenny Co., Avsry Island, La.), 1 ml/100 g body weight.
The rats were returned
to their cages (no food or water available) and 3 hr later the animals ~ere killed and the stomachs excised.
RESULTS CRS.
Bismuth subsallcylate slurry, at doses of 0,.2, 0.6, and 1.0 ml,
caused a dose-related inhibition of gastric hemorrhagic formation in response to CRS (Table I).
At the two higher dose-levels bismuth subsalicylate par-
ticles were found in the zumen and gastric mucosa regions of most stomachs examined 3-1/2 hr after dosing.
16
Pharmacological Research Communications, Vol. 10, No. 1, 1978 TABLE I EFFECT OF BISMUTH SUBSALIC~LATE SLURRY IN PREVENTING HEMORRHAGIC IZSIONS OF THE GASTR£C MUCOSA OF THE RAT INDUCED BY 3-HR COLD + RESTRAINT STRESS
Volume ml
Treatment
No. of rats
(+_ S.E.M. ) Mean no. of lesions /stomach
Control (distilled water)
0.2
I0
2.9 + 0.3
Control
0.6
I0
3.3 + 1.1
control
1.0
7
BismUth subsalicylate
0.2
I0
2.3 + 0.5
Bismuth subsalicylate
0.6
13
1.9 + 0.5
Bismuth subsalicylate
1.0
8
4.1+1.5
0.9 + 0.7 a
asignificantly different from control group; p
Aspirin and CRS,
AS shown in Table IX, bismuth subsalicylate slurry,
at 0.2, 0.6, and 1.0 mi, elicited a marked and significant dose-related reduction in the number of hemorrhagic lesions as compared to control.
Bismuth
subsalicylate particles were found in rat stomachs at all dose levels; they were most prevalent at 0.6 and 1.0 ml doses. Alcoh01-induced " gastric lesions.
Bismuth subsalic-llate slurry at 10 =,
30-, or 60-rain pretreatment intervals evoked dose-rela~-d protection of the gastric
mucosae
of rats following 1 or 3 ml of 50% ethyl alcohol (Table XII).
At a given dose of bismuth subsalicylate slurry, pretreatment time interval is inversely related to protection from lesion formation.
Particles of
bismuth subsalicylate were visible in the stomachs of treated rats at all doses and at all pretreatment intervals.
Pharmacclogical Research Communications,, Vol. 10, No. 1, 1978
17
TABLE II EFFECT OF BISLrOTH SUBSALICYLATE SLURRY IN PREVENTING HEMORRHAGIC LESIONS OF %~IE GASTRIC MUCOSA OF THE RAT INDUCED ASPIRIN AND 3-HR COLD + RESTRAINT STRESS
Treatment
Volume ml
NO. of rats
(t S.E.~. ) Mean no. of lesions /stomach
Control (distilled water)
0.2
8
9.0+1.5
Control
0.6
8
9.1 + 1.8
Control
1.0
8
7.0+0.5
Bismuth subsalicylate
0.2
8
3.4 +
Bismuth subsalicylate
0°6
8
2.6 + 0.8 a
Bismuth subsalicylate
1.0
8
2.1 + 0 . 8 a
0.9 a
asignificantly d~fferent from control group; p<0.05.
T abascolsauce-induce d lesions.
Bismuth subsalicylate, 0.2 and 0.6 ml,
caused a dose-related significant reduction in the number of hemorrhagic lesions induced by Tabasco sauce (Table IV).
Capsicum, the irritant subs~tance
derived from pepper, has been demonstrated to cause irritation and hemorrhage in human stomachs (Viranuvatti et al., 1972).
DISCUSSION Previously, Pepto-Bismol liquid was reported to protect the gastric mucosa of rats from hemorrhagic lesion formation in response to CRS, to a combination of aspirin and CRS, and to ethyl alcohol (Goldenberg et al., 1975).
In the present study, bismuth subsalicylate was found to hs the agent
responsible for the degree of protection afforded by Pepto-Bismol liquid.
0.2 0.6 1.0
pretreatment
30 rain pretreatment '
60 ~ n
4.3 + 0.7 b 1.5 ~ 0.7 b 0.9 ~ 0.3 b
3.3 + 1.5 b 0.7 ~ 0.5b 0.0 ~- 0.0 b
1.7 + 0.6 b 0.5 ~ 0.4 b 0.i ~ 0.I b
0.2 0.6 1.0
0.2 0.6 1.0
6.5 + 1.4 a
4.0 ~ i.ib 2.6 ? 0.6b
3.9 + 0.8 b
0.8 ~ 0.2 b
2,1 ~" o.sb
4.9 + 1.0 b
4.6 + 1.0 b 1.6 ~ 0.5 b 1.3 ~ 0.5 b
8.6 + 0.6
3 ml 50% ethyl alcohol Mean no. of lesions/stomach
l~0 rain p r e t r e a t m e n t
~ m! 50% eth~10 alc phol Mean no. of lesions/stomach
1.0
(ml)
Dose
bsi~ificantly different from control group; p<_O.05.
aM.e~n + S.E.M.
Bismuth subsalicylate slurry " "
v!
Bismuth subsalicylate slurry
slurry
Distilled water (control) Bismuth subsaliaylate
Treatment
EFFECT OF BISMU~q SUBSALICYLATE SLURRY ON GASTRIC HEMORRHAGIC LESIONS IN RATS INDUCED BY 50% ETHYL ALCOHOL
TABLE III
co
Pharmacological Research Communications, Vol. 10, No. 1, 1978
19
TABLE IV ACTION OF BISMUTH SUBSALIC~LATE SLURRY ON GASTRIC HEMORRHAGIC LESION FORMATION INDUCED BY TABASCO BRAND PEPPER SAUCE IN RATS
Treatment
Control (distilled water)
Volume ml
0,2-0.6
No. of rats
(+ S.E.Mo) (Mean no. of lesions /stomach
7
6.4 + 1.3
Bismuth subsallcylate
0.2
7
4.6 + 1.2
Bismuth subsalicylate
0.6
7
1 o7 + 0.6 a
asignificantly different from control group; p<0.05.
That is, bismuth subsalicy!ate caused significant dose-related protection of the rat gastric mucosae, regardless of ~at s~rain or sex, against various noxious factors known to lead to erosions or hemorrhagic lesions. Bismuth compounds have been described as forming a protective barrier in the stomach against noxious stimuli (Weiss and Serfontein, 1971).
Weiss
and Serfontein (1971) have proposed that the beneficial effects of a bismuth-protein-complex agent in treating patients with gastric and duodenal ulcers could be due to rapid covering of the ulcer surfaces with a protecting layer of insoluble, bismuth-containing-complex material.
In the present
study, particles of bismuth subsalicylate were found in the stomachs of rats exposed to the stressful situations.
Such findings suggest an interaction
between the bismuth subsalicylate and the factors responsible for lesion format/on, with resulting protection of the gastric mucosal barrier. Aspirin breaks ~ e
gastric mucosal barrier in animals and man (Rainsford,
1975~ Baskin et al., 1976).
Alcohol damages the stomach by sloughing off
the protective superficial mucosal cells, leading to rapid cell death
Pharmacological Research Communications, VoL 10, No. 1, 1978
20 (Rainsford, 1975).
Capsicum causes hemorrhagic lesions through its irritant
effect on the mucosa (Viranuvattl, 1972).
Since cyclic AMP is involved in
the control of cell permeability in the mucosa, the decrease of this nucleotide might be involved in ethanol- or aspirin-induced gastric n~cosal damage (Puurunen and Karppanen, 1975).
The exact mechanism of the protective
effect of bismu~% subsalicylate against these ulcerative factors remains to be elucidated.
Suffice it to say that the gastric mucosal barrier is posi-
tively reinforced by the administration of bismuth subsalicylate to withstand the induction of gastric erosions by a multltude of factors working through different ulcerogenic mechanisms.
REFERENCES Baskin, W.N., Ivey, K.J.~. Krause, W.J., Jeffrey, G.E. and Gemme!i, R.T. (1976). Ann. Int. Med. 85: 299. Brownlee, K.A.
(1965)
°
Statistical Theory and Methodology in Science and
Engineering, 2nd ed., John Wiley & Sons, Inc., New York, p 163-166. Goldenberg, M~M.
(1973). Life Sciences 12: 519.
Goldenberg, M.M., .Honkomp, L.J., Burrous, S.E. and Castellion, A.W.
(1975).
Gastroenterology 69. 636. Harvey, S.C.
(1970'). The Pharmacological Basis of Therapeutics, MacMillan,
New York, p 1002-1019. Puurunen, J. and Karppanen, H. (1975). Rainsford, K.D.
(1975) o
Life Sciences 16: 152:3.
Agents and Actions 5: 326.
Viranuvatti, V., Kalayasiri, C., ChearaniF O. and Plengvanit, V. (1972). Amer. J. Gastroent. 58: 225° Weiss, G. and Serfontein, W.J. (1971).
S. Afr. Med. J. 45: 467.