The effect of ethomerzol fumarate on the antioxidant system and lipid peroxidation of rat erythrocytes during mercury acetate poisoning

Original article

УДК 616-092.9:619-099:549.291.1

DOI: 10.57034/2618723X-2022-04-04

K.М. Shchepetkova¹*, Postgraduate student of the Department of Biological Chemistry, https://orcid.org/0000-0002-8250-4178
V.A. Kashuro^1,3,4, MD, Dr. Sci. (Med.), Associate Professor, Head of the Department of Biological Chemistry, https://orcid.org/0000-0002-7892-0048
E.B. Shustov^2,5, MD, Dr. Sci. (Med.), Chief Researcher, https://orcid.org/0000-0001-5895-688X
E.G. Batotsyrenova^1,2, PhD, Associate Professor, Associate Professor of the Department of Biological Chemistry,
https://orcid.org/0000-0003-3827-4579
E.N. Krasnikova¹, MD, PhD, Cand. Sci. (Chemistry), Associate Professor of the Department of Biological Chemistry

¹ Federal State Budgetary Institution of Higher Professional Education “St. Petersburg State Pediatric Medical University” of the Ministry of Healthcare of the Russian Federation,
194100, Russia, Saint Petersburg, Litovskaya str., 2;
² The Federal State-Financed Institution Golikov Research Clinical Center of Toxicology under the Federal Medical Biological Agency,
192019, Russia, Saint Petersburg, Bekhtereva str., 1;
³ The Herzen State Pedagogical University of Russia,
Russia, 191186, Russia, Saint Petersburg, Moika River embankment, 48;
⁴ Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal State Unitary Enterprise, Federal Medical Biological Agency of Russia,
188663, Russia, Leningrad region, Vsevolozhsky district, Kuzmolovsky settlement;
⁵ St. Petersburg State Chemical and Pharmaceutical University of the Ministry of Health Сare of Russia,
197376, Russia, St. Petersburg, Professor Popov str., 14, lit. A.

* E-mail: [email protected]

Keywords: Mercury acetate subchronic poisoning pharmacological correction etomerzol fumar salt

Acknowledgements

The study was performed without external funding.

For citation:

Shchepetkova K.М., Kashuro V.A., Shustov E.B., Batotsyrenova E.G., Krasnikova E.N. The effect of ethomerzol fumarate on the antioxidant system and lipid peroxidation of rat erythrocytes during mercury acetate poisoning. Laboratory Animals for Science. 2022; 4. https://doi.org/10.57034/2618723X-2022-04-04

Abstract

Mercury is one of the most dangerous heavy metals and poses a serious threat to human health. Even at low concentrations, mercury can damage the functions of many organs and tissues. By binding to the SH-groups of enzymes, mercury has an inhibitory effect on their activity, which leads to an excessive accumulation of reactive oxygen species and the development of oxidative stress. The redox balance in a living organism is maintained by a multilevel antioxidant system. Erythrocytes are protected from the action of reactive oxygen metabolites by various biological mechanisms, including low molecular weight antioxidants and enzymatic protection. A decrease in the antioxidant ability of erythrocytes can affect the systemic antioxidant defense of the whole organism. Elucidation of the mechanisms of formation of lesions under subchronic exposure to mercury and its compounds and the pharmacological correction of such disorders remains an important problem in modern medicine.

The aim of this study was to study the effect of etomerzole fumaric salt on the processes of lipid peroxidation, the parameters of the antioxidant system of rat erythrocytes under subchronic low-dose exposure to an aqueous solution of mercury acetate. Subchronic poisoning was modeled by a single daily administration of an aqueous solution of mercury acetate at a dose of 4 mg/kg to Wistar rats included in the control and experimental groups. After 30 days of administration of mercury acetate, the animals of the experimental group were divided into 2 subgroups. One subgroup underwent pharmacological correction by intragastric administration of an aqueous solution of etomerzole fumaric salt at a dose of 12.5 mg/kg for 14 days. The other subgroup received distilled water at the same time. The results of the study showed that the administration of the drug led to a decrease in the concentrations of diene conjugates and malondialdehyde in the hemolysate of erythrocytes of the experimental group of rats. The introduction of etomerzole fumarate to the animals of the experimental group contributed to a decrease in the activities of superoxide dismutase, glutathione peroxidase and glucose-6‑phosphate dehydrogenase, as well as an increase in the activity of glutathione transferase.

It has been established that the fumaric salt of etomersol has an antioxidant effect after subchronic mercury acetate poisoning.

Conflict of interest

The authors declare no conflict of interest.

Authors contribution

K.M. Shchepetkova — data collection, material processing, statistical data processing, collection and analysis of literary sources, text writing, text editing.
V.A. Kashuro — research management, research concept and design, text editing, approval of the manuscript for publication.
E.B. Shustov — text editing, approval of the manuscript for publication.
E.G. Batotsyrenova — research management, concept and design of the research, text editing, approval of the manuscript for publication.
E.N. Krasnikova — text editing.
All authors approved the version for publication.

References

Русецкая Н.Ю., Бородулин В.Б. Биологическая активность селеноорганических соединений при интоксикации солями тяжелых металлов // Биомедицинская химия. 2015. № 64(4). С. 449–461. [Rusetskaya N.Yu., Borodulin V.B. Biologicheskaya aktivnost’ selenoorganicheskikh soedinenii pri intoksikatsii solyami tyazhelykh metallov // Biomeditsinskaya khimiya. 2015. N. 64(4). P. 449–461. (In Russ.)].
Щепеткова К.М., Батоцыренова Е.Г., Литвиненко Л.А., Раменская Н.П., Кашуро В.А. Антиоксидантная система и перекисное окисление липидов в эритроцитах крыс при низкодозовом воздействии ацетатом ртути // Педиатр. 2022. Т. 13. № 2. С. 25–34. [Shchepetkova K.M., Batotsyrenova E.G., Litvinenko L.A., Ramenskaya N.P., Kashuro V.A. Antioksidantnaya sistema i perekisnoe okislenie lipidov v eritrotsitakh krys pri nizkodozovom vozdeistvii atsetatom rtuti // Pediatr. 2022. Vol. 13. N. 2. P. 25–34. (In Russ.)].
Кашуро В.А., Глушков С.И., Карпищенко А.И., Новикова Т.М., Глушкова Т.И., Минаева Л.В., Сибирев С.А. Состояние системы глутатиона в тканях паренхиматозных органов лабораторных животных при повторном введении циклофосфана // Нефрология. 2006. Т. 10. № 4. С. 82–86. [Kashuro V.A., Glushkov S.I., Karpishchenko A.I., Novikova T.M., Glushkova T.I., Minaeva L.V., Sibirev S.A. Sostoyanie sistemy glutationa v tkanyakh parenkhimatoznykh organov laboratornykh zhivotnykh pri povtornom vvedenii tsiklofosfana // Nefrologiya. 2006. Vol. 10. N. 4. P. 82–86. (In Russ.)].
Головко А.И., Батоцыренова Е.Г., Комов Ю.В., Хальчицкий С. Е., Кашуро В.А. Обзор лекарственных препаратов для коррекции нарушений ЦНС, развившихся в результате действия нейротоксикантов // Medline.ru. Российский биомедицинский журнал. 2022. Т. 23. № 1. С. 385–419. [Golovko A.I., Batotsyrenova E.G., Komov Yu.V., Khalchitsky S.E., Kashuro V.A. Obzor lekarstvennykh preparatov dlya korrektsii narushenii CNS, razvivshihsya v rezultate deistviya neirotoksikantov // Medline.ru. Rossiiskyi biomeditsinskii zhurnal. 2022. Vol. 23. N. 1. P. 385–419. (In Russ.)].
Кашуро В.А. Патогенетическое и диагностическое значение системы глутатиона в оценке цитотоксического действия противоопухолевых препаратов: автореферат диссертации на соискание ученой степени доктора медицинских наук / Военно-медицинская академия им. С.М. Кирова. Санкт-Петербург. 2009. [Kashuro V.A. Patogeneticheskoe i diagnosticheskoe znachenie sistemy glutationa v otsenke tsitotoksicheskogo deistviya protivoopukholevykh preparatov: avtoreferat dissertatsii na soiskanie uchenoi stepeni doktora meditsinskikh nauk / Voenno-meditsinskaya akademiya im. S.M. Kirova. Sankt-Peterburg. 2009. (In Russ.)].
Кострова Т.А., Батоцыренова Е.Г., Золотоверхая Е.А., Кубарская Л.Г., Кашуро В.А., Краснов К.А. Влияние виолуровой кислоты на антиоксидантную систему в отдаленный период после отравления тиопенталом натрия // Medline.ru. Российский биомедицинский журнал. 2021. Т. 22. С. 551–561. [Kostrova T.A., Batotsyrenova E.G., Zolotoverkhaya E.A., Kubarskaya L.G., Kashuro V.A., Krasnov K.A. Vliyanie violurovoi kisloty na antioksidantnuyu sistemu v otdalennyi period posle otravleniya tiopentalom natriya // Medline.ru. Rossiiskii biomeditsinskii zhurnal. 2021. Vol. 22. P. 551–561. (In Russ.)].
Болотова В.Ц., Болотина Ю.Д., Шустов Е.Б. Влияние этилтиобензимидазола фумарата на физическую работоспособность мышей в условиях одновременного гипоксического и гипертермического воздействия // Биомедицина. 2021. Т. 17. № S3. С. 139–143. [Bolotova V.Ts., Bolotina Yu.D., Shustov E.B. Vliyanie etiltiobenzimidazola fumarata na fizicheskuyu rabotosposobnost’ myshei v usloviyakh odnovremennogo gipoksicheskogo i gipertermicheskogo vozdeistviya // Biomeditsina. 2021. Vol. 17. № S3. P. 139–143. (In Russ.)].
Директива 2010/63/EU Европейского парламента и совета Европейского союза от 22.09.2010 по охране животных, используемых в научных целях. Гл. I, ст. 6. [Direktiva 2010/63/EU Evropeiskogo parlamenta i soveta Evropeiskogo soyuza ot 22.09.2010 po okhrane zhivotnykh, ispol’zuemykh v nauchnykh tselyakh. Gl. I, st. 6. (In Russ)].
Altman D.G. How to randomize // British medical journal. 1999. Vol. 319 (7211). Р. 703–704.
Рыбакова А.В., Макарова М.Н. Методы эвтаназии лабораторных животных в соответствии с европейской директивой 2010/63 // Международный вестник ветеринарии. 2015. № 2. С. 96–107. [Rybakova A.V., Makarova M.N. Metody ehvtanazii laboratornykh zhivotnykh v sootvetstvii s evropeiskoi direktivoi 2010/63 // Mezhdunarodnyi vestnik veterinarii. 2015. N. 2. P. 96–107. (In Russ)].
Зайцева М.А., Бонитенко Е.Ю., Иванов М.Б., Скобелев Д.О., Чечеватова О.Ю., Пикалова Л.В. Система обеспечения качества при проведении мультицентровых доклинических исследований // Фундаментальные исследования. 2014. Т. 7–5. С. 955–959. [Zajceva M.A., Bonitenko E.Ju., Ivanov M.B., Skobelev D.O., Chechevatova O.Ju., Pikalova L.V. Sistema obespechenija kachestva pri provedenii mul’ticentrovyh doklinicheskih issledovanij // Fundamental’nye issledovanija. 2014. Vol. 7–5. P. 955–959. (In Russ.)].
Adedara I.A., Ebokaiwe A.P., Farombi E.O. Tissues distribution of heavy metals and erythrocytes antioxidant status in rats exposed to Nigerian bonny light crude oil // Toxicology and Industrial Health. 2011. Vol. 29 N. 2. Р. 162–168.

Received: 2022-09-20

Reviewed: 2022-10-26

Accepted for publication: 2022-11-09

You may be interested

Allergy to laboratory rodents: the underestimated problem
In the present review, we discuss the problem of hypersensitivity to laboratory animal allergens, which affects both animal caretakers and research personnel. Biological characteristics of the main allergens released by laboratory rodents are presented, as well a
Diet-induced models of metabolic disorders. Report 7: Experimental osteoporosis
The high incidence of osteoporosis dictates the need to find ways to effectively prevent and treat it, including in animal experiments.
Determination of reference intervals of creatinine clearance in laboratory animals
The assessment of renal function is an important part of monitoring the health of laboratory animals in preclinical studies. One of the most important indicators for the assessment of renal function is serum creatinine concentration and endogenous creatinine clearance.
Impedansometry as an estimating method of tertiary endpoint in experimental modeling of alimentary impairments
In preclinical practice, methods for assessing the body composition of laboratory animals are used, such as: computerized tomography, quantitative magnetic resonance, dual-energy X-ray absorptiometry, gravimetric method, bioimpedance spectroscopy method (hereinafter r
Comparative Morphology of Human and Laboratory Animals
Knowledge the characteristics of the morphological structure, the main structural and functional components of human skin and laboratory animals is the foundation of rational planning of pharmacological and toxicological preclinical studies of skin dosage forms in aspect.
Effect of deltametrin (Delcid) on the reproductive ability of laboratory mice
The key to successful research on laboratory animals is their quality. In the conditions of the domestic market of laboratory animals, there are a number of constraining factors, and it is almost impossible to purchase animals in the required volume.