Activity of enzymes destroying extracellular nucleotides in the tissues of rats with the valproate model of autism

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Abstract

BACKGROUND: Ectonucleotidases hydrolyze extracellular nucleotides and thus can control the effect of these substances on purinergic P1 and P2 receptors.

AIM: To evaluate the activity of ectonucleotidases in the smooth muscle tissues of internal organs of 9-month-old rats with the valproate model of autism using high-performance liquid chromatography.

MATERIAL AND METHODS: Autism was modeled in outbred Wistar rats by administering valproic acid (500 mg/kg) subcutaneously to pregnant females on days 12–13 of pregnancy. The born offspring were used in the study when the rats reached 270±8 days. Animals were guillotined under light ether anesthesia, the bladder, uterus, vas deferens, and duodenum were isolated, and smooth muscle tissue samples were prepared. Total ectonucleotidase activity was determined by incubating tissue samples with adenosine triphosphate (reaction substrate) for 10 minutes with further assessment of the content of the substrate and reaction products (adenosine diphosphate, adenosine monophosphate) in the incubate using high-performance liquid chromatography. Mathematical and statistical processing of the results was carried out using Microsoft Excel and IBM SPSS Statistics 26.0 software. Group comparisons were made using the nonparametric Mann–Whitney U test. Differences were considered significant at p <0.05.

RESULTS: In rats with the valproate model of autism, the activity of ectonucleotidases in the smooth muscle tissues of the vas deferens (609.5±153.9) and uterus (232.7±2) was significantly lower than control values (2114.6±524.3, p=0.040; 539.6±63.5, p=0.010, respectively). In the duodenum (1808.4±184.5) and bladder (1021.3±280.7) we did not find a significant difference compared to the control values (2115.0±393.3, p=0.712; 2302.3±615.8, p=0.274, respectively). This study allows us to evaluate the possible contribution of purinergic transmission to the changes we found earlier in the contractile activity of smooth muscle tissue in rats with the valproate model of autism.

CONCLUSION: In 9-month-old rats with a model of autism, the activity of ectonucleotidases in the smooth muscle tissues of the reproductive organs is reduced; no such changes were found in the tissues of the intestines and bladder.

About the authors

Daria V. Ivanova

Kazan State Medical University

Author for correspondence.
Email: ivanovadv96@yandex.ru
ORCID iD: 0009-0002-0158-5971

Assist., Depart. of Pharmacology

Russian Federation, Kazan, Russia

Rinat A. Khabirov

Kazan (Volga Region) Federal University

Email: rinat.habirov.99@yandex.ru
ORCID iD: 0009-0008-9564-8171

M.D., Resident, Depart. of Internal Medicine

Russian Federation, Kazan, Russia

Ayrat U. Ziganshin

Kazan State Medical University

Email: ayrat.ziganshin@kazangmu.ru
ORCID iD: 0000-0002-9087-7927

M.D., D. Sci. (Med.), Prof., Head of Depart., Dept. of Pharmacology

Russian Federation, Kazan, Russia

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2. Fig. 1. Duodenal ectonucleotidase activity of rats in a valproate model of autism at 9 months of age. Data are presented as M ± m. Control (n = 12); experiment (n = 11); p = 0.712

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3. Fig. 2. Ectonucleotidase activity in the urogenital system of 9-month-old rats in a valproate model of autism. Data are presented as M ± m. A. Seminal duct: control (n = 15), experiment (n = 10), *p = 0.040. B. Bladder: control (n = 19), experiment (n = 12), p = 0.274. C. Uterus: control (n = 6), experience (n = 19), *p = 0.010 compared to the control group

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