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PRECLINICAL STUDY OF PHARMACOLOGICAL ACTIVITY OF ENTEROSORBENTE ON THE BASIS OF MONTMORILLONITE

Introduction: At present, enterosorbents based on mineral raw materials are in high demand among the population. However, there are no enterosorbents on the Russian pharmaceutical market on the basis of domestic mineral raw materials.

Objectives: to study the pharmacological activity of enterosorbent based on montmorillonite of Russian origin under experimental conditions.

Methods: The methodological approach was based on the implementation of a complex of theoretical, pharmacological, toxicological, histological, biochemical, statistical methods. Models of experimental diarrhea, acute and toxic liver damage, acute experimental pancreatitis were selected.

Results and discussion: Enterosorbent based on montmorillonite Crim_04 has a dose-dependent antidiarrhoeal effect, which is manifested in an increase in the time of onset of diarrhea from 50.4% to 82.6% with various models of diarrhea, a reduction in the number of defecations from 50.4% to 64.4% liquid in them. Enterosorbent on the basis of montmorillonite has a high sorption activity to E.coli enterotoxin, inhibiting the outflow of fluid into the luminal cavity by 95.1%. In addition, the use of enterosorbent Crim_04 significantly improves biochemical indices in the blood serum of rats when modeling acute and chronic liver damage and acute pancreatitis.

Conclusion: The enterosorbent under the Crim_04 cipher has a dose-dependent anti-diarrhea, detoxification activity, high sorption activity for E.coli enterotoxin, high therapeutic efficacy in experimental pancreatitis, most pronounced at a dose of 3320 mg / kg. It can be recommended for further complex toxicological studies and clinical trials.

Иллюстрации

Fig. 1A. Dose-dependent influence of enterosorbent under the Crim_04 cipher for the time of onset of serotonin-induced diarrhea in mice (minutes).

Note: + - for p <0.05 in comparison with the group of intact animals; * - at p <0.05 in comparison with the control group; a - p <0.05 in comparison with the group Crim_04 in a dose of 880 mg/kg; b - p <0.05 in comparison with the group Crim_04 in a dose of 1660 mg/kg; # - p <0.05 in comparison with the group of loperamide.

Fig. 1B. Dose-dependent influence of enterosorbent under the code Crim_04 on the number of defecations in serotonin-induced diarrhea in mice (number).

Note: + - for p <0.05 in comparison with the group of intact animals; * - at p <0.05 in comparison with the control group; a - p <0.05 in comparison with the group Crim_04 in a dose of 880 mg/kg; b - p <0.05 in comparison with the group Crim_04 in a dose of 1660 mg/kg; # - p <0,05 in comparison with the group of loperamide.

Fig. 1C. Dose-dependent influence of enterosorbent under the code Crim_04 on the consistency of feces in serotonin-induced diarrhea in mice (cond.

Note: + - for p <0.05 in comparison with the group of intact animals; * - at p <0.05 in comparison with the control group; a - p <0.05 in comparison with the group Crim_04 in a dose of 880 mg/kg; b - p <0.05 in comparison with the group Crim_04 in a dose of 1660 mg/kg; # - p <0,05 in comparison with the group of loperamide.

Fig. 2. Histological structure of the ileum in mice against the background of modeling serotonin-induced diarrhea (microphot × 100).

Note: A - intact animals; B - control group; C - enterosorbent Crim_04 in a dose of 1660 mg/kg; D - enterosorbent Crim_04 in a dose of 3320 mg/kg; E - Enterosorbent "Smecta" 1660 mg/kg; F - loperamide 10 μg/kg. Okr. hematoxylin and eosin.

Fig. 3. Influence of the enterosorbent under the Crim_04 cipher on the ratio of the length of the villi to the width of the villi and the length of villi to the depth of crypt in the small intestine of mice when simulating serotonin-induced diarrhea (conv. Units).

Note: * - for p <0.05 in comparison with the group of intact animals; ** - at p <0.05 in comparison with the control group; a - p <0.05 in comparison with the group Crim_04 in a dose of 880 mg/kg

Fig. 4. Influence of the enterosorbent under the Crim_04 cipher in comparison with the Smecta preparation on the dilatation index on the isolated bowel loop model (mg/cm).

Note: * - for p <0.05 in comparison with the control group; ** - at p <0.05 in comparison with TCET; a - at p <0,05 in comparison with enterosorbents in a dose of 50 mg/ml; b - at p <0,05 in comparison with enterosorbents in a dose of 100 mg/ml

Fig. 5. The dose-dependent effect of the enterosorbent under the Crim_04 cipher in comparison with the Smecta preparation on the severity of the inhibition of fluid flow into the lumen of the gut on the model of the isolated bowel loop (%).

Note: * - at p <0,05 in comparison with enterosorbents in a dose of 50 mg/ml; ** - at p <0,05 in comparison with enterosorbents in a dose of 100 mg/ml

Fig. 6A. Influence of application of enterosorbent under the code Сrim_04 on the activity of AsAT and AlAT in modeling acute toxic liver damage in rats (U/l).

Note: ** - p <0.05 - in comparison with the control; * - p <0.05 - in comparison with intact

Fig. 6B. Effect of the use of enterosorbent under the code Сrim_04 on the activity of alkaline phosphatase in the blood of rats when modeling acute toxic damage to the liver (U/l).

Note: ** - p <0.05 - in comparison with the control; * - p <0.05 - in comparison with intact

Fig. 6C. Effect of application of enterosorbent under the code Сrim_04 on the level of urea in the blood of rats when modeling acute toxic damage to the liver (mmol/l).

Note: ** - p <0.05 - in comparison with the control; * - p <0.05 - in comparison with intact

 Fig. 6D. Effect of the use of enterosorbent under the code Сrim_04 on the level of creatinine in the blood of rats when modeling acute toxic damage to the liver (μmol/l).

Note: ** - p <0.05 - in comparison with the control; * - p <0.05 - in comparison with intact

Fig. 6E. Effect of application of enterosorbent under the code Сrim_04 on the level of total bilirubin in the blood of rats when modeling acute toxic damage to the liver (μmol/l).

Note: ** - p <0.05 - in comparison with the control; * - p <0.05 - in comparison with intact

Fig. 7. Morphological examination of liver tissue (microphotography × 100).

Note: A - group of intact animals; B - control group; C - enterosorbent under the cipher of Crim_04 in a dose of 385 mg/kg; D - enterosorbent under the code number Crim_04 in a dose of 770 mg/kg; E - enterosorbent under the cipher of Crim_04 in a dose of 1500 mg/kg; F - the drug "Smecta" in a dose of 770 mg/kg

Table 1. Influence of enterosorbent under the cipher of Crim_04 in comparison with the "Smecta" preparation on the biochemical parameters of blood of rats against the background of modeling of acute L-arginine-induced pancreatitis 

Fig. 8. Morphological examination of pancreatic tissue (microphoto × 100).

Note: A - group of intact animals; B - control group; C - enterosorbent under the cipher of Crim_04 in a dose of 1500 mg/kg

DOI: 10.18413/2313-8971-2017-3-3-37-54
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