Effect of dimephosphone in a course administration on the mechanical activity of the intestine of rats with an autism model

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Abstract

BACKGROUND: Gastrointestinal tract dysfunctions are a very common problem in patients with autism spectrum disorders, which aggravates the underlying course of the disease, and therefore there is a need to find safe drugs to correct gastrointestinal dysfunctions.

AIM: Evaluation of intestinal contractile activity in rats with an autism model after a course of intragastric administration of dimephosphone.

MATERIAL AND METHODS: The mechanical activity of the duodenum and ileum of rats with the valproate model of autism after the administration of dimephosphone was studied in vitro. To model autism, female rats were given a single subcutaneous injection of sodium valproate at a dose of 500 mg/kg in the withers area on the 13th day of pregnancy. The offspring of these rats were divided into two groups. The experimental group of rats (n=12) was given dimephosphone at a dose of 50 mg/kg for 30 days, starting from the age of 2 months, control rats (n=12) were given physiological saline in an equal volume. Another group of rats was intact (n=9), which were born from female rats not exposed to valproic acid. The effect of carbachol (10–8–10–5 M), ATP (10–7–10–4 M), 2-methylthio-ATP (10–7–10–5 M) and electrical stimulation (1–5 Hz) on the mechanical activity of isolated intestinal smooth muscle preparations was assessed. Statistical processing was performed in IBM SPSS Statistics 26.0 using one-way analysis of variance.

RESULTS: It was found that in rats with autism modeling, carbachol-induced intestinal contractions and ATP-induced intestinal relaxation increased. A course of intragastric administration of dimephosphone for 30 days normalized these changes, which became indistinguishable from the corresponding indices in intact animals. Thus, ATP at a concentration of 10–4 caused relaxation of the smooth muscles of the duodenum of rats with autism modeling after a course of dimephosphone administration by 77.1±14.7%, which significantly differed from the corresponding indices in control animals — 34.4±9.4% (p <0.05) and did not differ from the indices in intact rats. Similar changes occurred in the mechanical activity of the ileum. Intestinal relaxation in rats caused by 2-methylthio-ATP did not change significantly either in the control or in the group of animals receiving dimephosphone.

CONCLUSION: Dimephosphone, when administered intragastrically, normalizes the disturbances in the mechanical activity of the intestines of rats with an autism model.

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About the authors

Ainur M. Zyapbarov

Kazan State Medical University

Author for correspondence.
Email: zyapbarov43@gmail.com
ORCID iD: 0000-0001-8388-9172
SPIN-code: 6588-4813

Postgrad. Stud., Depart. of Pharmacology

Russian Federation, Kazan

Daria V. Ivanova

Kazan State Medical University

Email: ivanovadv96@yandex.ru
ORCID iD: 0009-0002-0158-5971
SPIN-code: 3512-4452

Assistant, Depart. of Pharmacology

Russian Federation, Kazan

Alexandra S. Bakanova

Kazan State Medical University

Email: bakanova.alexandra@yandex.ru
ORCID iD: 0000-0002-2430-3554

student

Russian Federation, Kazan

Ayrat U. Ziganshin

Kazan State Medical University; Russian Medical Academy of Continuous Professional Education

Email: ayrat.ziganshin@kazangmu.ru
ORCID iD: 0000-0002-9087-7927
SPIN-code: 9723-2491

MD, Dr. Sci. (Med.), Prof., Head of Depart., Depart. of Pharmacology; Prof., Depart. of General Pathology and Pathophysiology

Russian Federation, Kazan; Moscow

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2. Fig. 1. Dimephosphone effect in a course of administration (50 mg/kg per day intragastrically for 30 days) on the contraction of isolated preparations of the duodenum (a) and ileum (b) longitudinal muscles of 3-month-old rats with a model of autism, induced by carbachol. The results are presented as M±m, n=6–10. *p <0.05 compared with intact animals

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3. Fig. 2. Dimephosphone effect in course administration (50 mg/kg per day intragastrically for 30 days) on the relaxation of carbachol-tonized isolated preparations of the duodenum longitudinal muscles of 3-month-old rats with a model of autism, induced by ATP. Results are presented as M±m, n=6–10. *p <0.05 compared to intact animals

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4. Fig. 3. Dimephosphone effect in course administration (50 mg/kg per day intragastrically for 30 days) on the relaxation of carbachol-tonized isolated preparations of the ileum longitudinal ¬muscles of 3-month-old rats with a model of autism, induced by ATP. Results are presen¬ted as M±m, n=6–10. *p <0.05 compared to intact animals

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5. Fig. 4. Dimephosphone effect in a course of administration (50 mg/kg per day intragastrically for 30 days) on the relaxation of carbachol-tonized isolated preparations of the duodenum (а) and ileum (b) longitudinal muscles of 3-month-old rats with a model of autism, induced by 2-methylthio-ATP (2-meATP). Results are presented as M±m, n=6–10

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6. Fig. 5. Dimephosphone effect in a course of administration (50 mg/kg per day intragastrically for 30 days) on the relaxation of carbachol-tonized isolated preparations of the duodenum (а) and ileum (b) longitudinal muscles of 3-month-old rats with a model of autism, caused by stimulation with an electric field of different frequencies. The results are presented as M±m, n=6–10. *p <0.05 compared with intact animals

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