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UDC 615.327:616.33-002.44
INFLUENCE OF MINERAL WATER ON THE COURSE OF EXPERIMENTAL GASTROPATHY
1 A.N. Sysin Research Institute of Human Ecology and Environmental Health, Moscow
2 I.M. Sechenov First Moscow State Medical University, Moscow
3 Altai State Medical University, Barnaul
G.G. Onishchenko 2, Yu.A. Rakhmanin 1, I.P. Saldan 3
The study was carried out in two groups of male Wistar rats: control (modeling of gastric ulcer disease) and experimental (modeling gastric ulcer + prophylactic seven-day use as a drink in free access to mineral water). The rats were euthanized, the stomachs extracted and the effectiveness of the gastroprotective action by macro and microscopic examination was evaluated.
The results of the study showed that in animals that received mineral water, as compared to the control of the disease, the amount of erosions of the gastric mucosa and the Pauls Index decreased by 3.3 times, the density of the inflammatory infiltrate decreased by 2.5 times and the thickness of the mucous membrane of the stomach increased by 1.3.
Thus, the seven-day use of mineral water as a drink in free access is accompanied by a significant simplification
of the experimental «indomethacin» ulcer in rats.
Key words: mineral water, experimental gastropathy, prophylaxis.
Gastritis and gastric ulcer continue to be one of the most common pathologies of the gastrointestinal tract [1]. Modern medicine has significantly advanced its capabilities in the treatment and prevention of gastropathy. There are a number of effective drugs with proven antiulcerogenic effect. Their use in accordance with generally accepted prescribing regimens makes it possible to achieve significant success in the treatment of gastritis and gastric ulcers [2].
At the same time, it is obvious that the issues of food and drink hygiene have a high relevance in the field of non-drug support of such patients. The scientifically based use of special drinking regimens may contribute to delaying the recurrence of gastropathy and to general improvement in the quality of life of patients. In this context, the attention of hygienists continues to be attracted by mineral and medicinal-table waters [3]. The study of their antiulcerogenic properties can make a significant contribution to the development of medical prevention and rehabilitation of patients with gastric ulcer and gastritis.
Altai Krai, due to its unique natural diversity of bioresources, possesses numerous sources of mineral waters that can potentially be used in gastroenterology. We were interested in studying the effect of mineral water extracted from the wells in Altai Krai on the course of experimental gastropathy in animals, which was the purpose of this study.
Materials and methods
The study was conducted on 20 male Wistar rats aged 2-3 months and weighing 250-280 g, divided equally into two groups: control (modeling of gastric ulcer) and experimental (model-
ing of gastric ulcer + preventive seven-day intake of "Zavyalovskaya" mineral water as a drink in free access). Animals were kept in standard conditions. The studies were carried out in compliance with the principles of humanity set forth in the directives of the European Community (86/609 / EEC) and the Helsinki Declaration, in accordance with the "Rules for work with experimental animals".
The non-steroidal anti-inflammatory drug in-domethacin was used as an ulcer-forming factor. The model of indomethacin damage to the stomach of rats was reproduced by a single intragastric administration of indomethacin at a dose of 60 mg/kg in 1 ml of saline. Before the administration of indomethacin, 7 ml of distilled water was intragastrically administered to the control group for 7 days. Under similar conditions for 7 days, animals of the experimental group were given "Za-vyalovskaya" mineral water as a drink in free access. 6 hours after the administration of the ulcer-forming factor, the rats were euthanized, the stomachs were removed, washed in distilled water, the material was fixed in a solution of 10% neutral formalin and the effectiveness of the gastroprotective action was assessed by macro- and microscopic examination.
Histological preparations were stained with hematoxylin and eosin. Histochemical detection of neutral mucopolysaccharides was performed using the Schiff reaction, acid mucopolysaccharides were detected using alcian blue staining (pH 2.5). The density of the inflammatory infiltrate was calculated in 1 mm2 using Avtandilov G.G. ocular grid. Morphometric measurements of the gastric mucosa (GM) were performed using the morphometric program Image Tool 3.0. The Pauls index was calculated by multiplying the average
number of destruction in the stomach per animal by the percentage of lesions in the group and dividing by 100%.
Statistical analysis was performed using the program Statistica 6.0. Results are presented as mean values (M) and standard error of the mean (± m). Statistical processing of the results was performed using the non-parametric Mann-Whitney test. Differences were considered significant when the validity coefficient value was p <0.05 [4].
Results and discussion
The results of the morphological study showed, that in animals of the control group, in the gastric mucosa (GM), there was a phenomenon of pronounced erosive gastritis. In a macroscopic study, the surface of GM looked bumpy with clearly visible destructive changes in the form of pulverized hemorrhages, surface erosion, point and strip-like ulcers and the phenomenon of hyperemia. Destructive changes were detected in all 10 experimental
animals of the control group. The number of ulcers and erosions in the stomach varied from 8 to 17, averaging 13.0 ± 1.6. Pauls index was 13.
According to the results of a microscopic study, it was established that GM looked atro-phic, the glandular and pathogenic epithelium was in a state of degeneration. The thickness of GM was 285.9 ± 10.3 microns. In histochemical studies using the Schick method, the columnar epithelium of the superficial divisions of GM fluid showed a weak reaction to neutral mucopolysaccharides. At the same time, acid mucopolysaccharides were poorly expressed in the cells of the deep sections of the gastric fossae. Necrotic changes in the ulcers reached the muscle layer. The bottom of the ulcers was represented by fibrin and purulent-necrotic masses (Figure 1). The density of the inflammatory infiltrate in the submucosal layer was 4,704.0 ± 313.3 cells in 1 mm2. Inflammatory infiltrate is represented by lymphocytes, plasma cells and a large number of neutrophils.
Figure 1 - Surface erosion in GM of rats by exposure to indomethacin. Stained with hematoxylin and eosin. Zoom x 100.
Against this background, in animals that received mineral water, the macroscopic GM on most sites looked even and smooth, in some areas weakly expressed destructive changes in the form of dust-like hemorrhages and small point erosions are determined. Such destructive changes were found in all 10 animals of the experimental group. The number of erosions was from 2 to 8, on average - 4.0 ± 0.9, which was 3.3 times less than in the control of the disease (p <0.001). The Pauls index similarly decreased relative to the control group and amounted to 4 (p <0.001).
Microscopic examination of GM in rats of the experimental group revealed signs of mi-
nor atrophy (Figure 2). The thickness of GM increased relative to the control of the disease by 1.3 times and amounted to 358.9 ± 10.8 ^m (p <0.01). In histochemical studies using the Schick method, the columnar epithelium of the superficial divisions of GM fluids gave a focal pronounced reaction to neutral mucopolysaccharides. Acid muco-polysaccharides were moderately detected in cells of the deep sections of the gastric fossae. Mild inflammation was observed in the submucosal layer. The density of the inflammatory submucosal infiltrate in animals of the experimental group was 2.5 times less than in the control of the disease, amounting to 1872.0 ± 225.7 mm2 (p <0.001).
Figure 2 - Signs of atrophy and lack of erosion by the use of "Zavyalovskaya" mineral water. Stained with hematoxylin and eosin. Zoom x 100.
Thus, in the course of the study, a pronounced gastroprotective effect exerted by mineral water when consumed as a free-access drink by experimental "indomethacin" ulcer was established. This was evidenced by a significant decrease in the number and aggressiveness of erosion of GM, a decrease in the density of inflammatory infiltrate and an increase in the thickness of GM of rats compared to the control of the disease.
As is known, indomethacin is a non-steroidal anti-inflammatory agent, the basis of the mechanism of which pharmacological activity is the ability to inhibit cyclooxygenase and disrupt the synthesis of prostaglandins, including the so-called gastroprotective prostaglandins that regulate the synthesis of protective mucus in the stomach. Under its influence in the stomach, the synthesis of protective mucus is weakened, which leads to the damage of GM by hydrochloric acid produced in the stomach, and thus ulcerative damage to the stomach develops [5]. According to the manufacturer, the water is chloride-sulphate calcium-magnesium-sodium with a salinity of 4.5 - 6.5 g/l. High content of Mg2+ cations is especially noted. It is possible that, at least in part, this can explain the high gastroprotective activity of water identified in our experiments. It is well known, that magnesium ions in the stomach neutralize hydrochloric acid, thereby weakening its aggressive effect on GM. It should be added, that similar results regarding the antiulcerogenic action of magnesium salts have been obtained by other researchers [6].
Conclusion
The seven-day use of mineral water as a free-access drink is accompanied by a significant relief in experimental "indomethacin" ulcers in rats, as evidenced by a significant decrease in the number and aggressiveness of GM erosion, a decrease in the density of inflammatory infiltrate and an increase in the GM thickness.
References
1. Graham D.Y. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer. World J Gastroenterol. 2014; 20(18): 5191-204.
2. Oshima T., Miwa H. Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases. J Neu-rogastroenterol Motil. 2018; 24(3): 334-344.
3. Razumov A.N., Surkov N.V., Frolkov V.K., Ziniakov N.T. Therapeutic and preventive effects of sulfate-chloride-sodium mineral water in experimental gastric ulcer. Vopr Kurortol Fizioter Lech Fiz Kult. 2009; (3): 22-5.
4. Khafaziyanova R.Kh., Burikin I.M., Ale-yeva G.N. Mathematical statistics in experimental and clinical pharmacology. Kazan: Meditsina; 2006.
5. Usmanova Sh.E., Yakubov A.V. The relationship of some aggressive-protective factors in the gastric mucosa with indomethacin-in-duced gastropathy and ways to correct it. Cardiovascular Therapy and Prevention. 2014; 13(S2): 120.
6. Adewoye E.O., Salami A.T. Anti-ulcero-genic mechanism of magnesium in indomethacin induced gastric ulcer in rats. Niger J Physiol Sci. 2013;28(2):193-9.
Contacts
Corresponding author:
Saldan Igor Petrovich, Doctor of medical Sciences, Professor, Rector of the Altai State Medical University, Barnaul.
656038, Barnaul, Lenina Prospekt, 40. Tel.: (3852) 566800. E-mail: [email protected]
Author information
Onishchenko Gennady Grigoryevich, Academician of the RAS, Doctor of Medical Sciences, Professor, Head of the Department of human ecology and en-
vironmental health of I.M. Sechenov First Moscow
State Medical University, Moscow.
119991, Moscow, Ul. Trubetskaya, 8, b.2.
Tel.: (499) 248-05-53.
E-mail: [email protected]
Rakhmanin Yury Anatolyevich, Academician
of the RAS, Doctor of Medical Sciences, Professor,
Head of A.N. Sysin Research Institute of Human
Ecology and Environmental Health, Moscow.
119121, Moscow, Ul. Pogodinskaya, 10, b.1.
Tel.: (495) 5406171.
E-mail: [email protected]
