Study of the effect of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)- 4H-1,2,4-triazole-3-yl)thio)acetate toxic doses on rats heart tissue

Authors

DOI:

https://doi.org/10.14739/2409-2932.2024.2.300859

Keywords:

1,2,4-triazole, rats, heart tissue, toxic action

Abstract

Analysis of medicinal product safety is an important stage on the way to the entry of a synthetic compound into the pharmaceutical market. Along with the study of blood composition, scientists are actively analyzing the effect of toxic doses on the tissues of internal organs. Analyzing the toxic effect of compounds on heart tissue allows us to find out what damage substances can cause, which can have a direct impact on human health. Today, 1,2,4-triazole derivatives are very relevant and a huge number of publications is a confirmation of this.

The aim of the work was to analyze the effect of toxic doses of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate on rats heart tissue.

Materials and methods. Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate (ASP) was selected as the subject of investigation and administered intragastrically in the form of a suspension with purified water using a specialized metal probe. The toxic effect on tissues was analyzed using doses of 1000 mg/kg, which is 10 times higher than a single dose typically used in pharmacological activity studies, and 5000 mg/kg, which represents the limit for determining acute toxicity and the maximum dose within the fourth class of toxicity, considering the route of administration, provided that this dose does not result in the death of the animal.

Analysis of the effect of toxic doses of ASP was performed on 12-month-old purebred male rats kept under standard conditions. Rat heart tissues were fixed for further histological examination in a 10 % formaldehyde solution, dehydrated in alcohols of increasing strength, and embedded in paraffin.

Results. Macroscopic and microscopic analysis of rat heart tissue was carried out. The research shows the histological results of deviations from the norm for a group of rats that were injected with substances in the studied doses.

Conclusions. The effect of toxic doses of ASP on rat heart tissue was analyzed. For a dose of 1000 mg/kg, local signs of protein dystrophy of cardiomyocytes and single loci of hemorrhages are observed. As for the dose of 5000 mg/kg, the effect of the substance on the heart tissue is more profound and is determined by the selective damage of cardiomyocytes with the loss of lumbar striation and the acquisition of a wave-like shape, full blood is observed in the ectasized capillaries.

Author Biographies

A. A. Safonov, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, Associate Professor of the Department of Toxicological and Inorganic Chemistry

O. I. Panasenko, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, DSc, Professor, Head of the Department of Toxicological and Inorganic Chemistry

N. A. Al Khalaf, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, Senior Lecturer of the Department of Toxicological and Inorganic Chemistry

References

Gupta PK. Target Organ Toxicity. In: Problem Solving Questions in Toxicology: Cham: Springer International Publishing; 2020. p. 83-117. doi: https://doi.org/10.1007/978-3-030-50409-0

Sameliuk Y, Al Zedan F, Kaplaushenko T. 1,2,4-triazole derivatives in medicine and pharmacy and application prospects. Journal of Faculty of Pharmacy of Ankara University. 2021;45(3):598-614. doi: https://doi.org/10.33483/jfpau.885888

Shcherbyna R. Microwave-assisted synthesis of some new derivatives of 4-substituted-3-(morpholinomethyl)-4H-1,2,4-triazole-5-thioles. Journal of Faculty of Pharmacy of Ankara University. 2019;43(3):220-9. doi: https://doi.org/10.33483/jfpau.533166

Safonov A. Microwave synthesis of new N-R-3-(alkylthio)-5-(thiophen-2-ylmethyl)-1,2,4-triazol-4-amines. Journal of Faculty of Pharmacy of Ankara University. 2020;44(1):89-98. doi: https://doi.org/10.33483/jfpau.620599

Dovbnia D, Frolova Y, Kaplaushenko A. A study of hypoglycemic activity of acids and salts containing 1,2,4-triazole. Ceska Slov Farm. 2023;72(3):113-24.

Sameliuk Y, Kaplaushenko A, Nedorezaniuk N, Ostretsova L, Diakova F, Gutyj B. Prospects for the search for new biologically active compounds among the derivatives of the heterocyclic system of 1, 2, 4-triazole. Hacettepe University Journal of the Faculty of Pharmacy. 2022;42(3):175-86. doi: https://doi.org/10.52794/hujpharm.1019625

Shcherbyna R, Parchenko V, Varynskyi B, Kaplaushenko A. The development of HPLC-DAD method for determination of active pharmaceutical ingredient in the potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio) acetate substance. Current Issues in Pharmacy and Medical Sciences. 2019;32(1):5-9. doi: https://doi.org/10.2478/cipms-2019-0001

Frolova Y, Kaplaushenko A, Nagornaya N. Design, synthesis, antimicrobial and antifungal activities of new 1,2,4-triazole derivatives containing 1H-tetrazole moiety. Journal of Faculty of Pharmacy of Ankara University. 2020;44(1):70-88. doi: https://doi.org/10.33483/jfpau.574001

Shcherbyna R. An investigation of the pharmacokinetics and potential metabolites of potassium 2-((4-amino-5-(morfolinometyl)-4H-1,2,4-triazol-3-yl)thio) acetate on rats. Journal of Faculty of Pharmacy of Ankara University. 2020;44(2):233-41. doi: https://doi.org/10.33483/jfpau.681611

Shcherbyna R, Vashchyk Y. The research of 1,2,4-triazole derivatives hepatoprotective activity under tetracycline and infectious hepatitis. Journal of Faculty of Pharmacy of Ankara University. 2019;43(2):135-46. doi: https://doi.org/10.33483/jfpau.487173

Gotsulya A. Synthesis and antiradical activity of alkyl derivatives of 5-(5-methyl-1H-pyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol. Journal of Faculty of Pharmacy of Ankara University. 2020;44(2):211-9. doi: https://doi.org/10.33483/jfpau.616116

Gotsulya A, Zaika Y, Brytanova T. Synthesis, properties and biological potential some condensed derivatives 1,2,4-triazole. Journal of Faculty of Pharmacy of Ankara University. 2022;46(2):308-21. doi: https://doi.org/10.33483/jfpau.971602

Samelyuk Y, Kaplaushenko A. Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, Containing methoxyphenyl substituents at c5atoms, Their antipyretic activity, Propensity to adsorption and acute toxicity. Journal of Chemical and Pharmaceutical Research. 2014:6(5):1117-21.

Safonov AA, Panasenko OI. Synthesis, antimicrobial and antifungal activity of 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles. Current issues in pharmacy and medicine: science and practice. 2022;15(3):235-40. doi: https://doi.org/10.14739/2409-2932.2022.3.264691

Bondarenko LB, Voronina A K, Shayakhmetova HM, Blazhchuk IS, Karatsuba TA, Kovalenko VM. [Study of essential phоspholipids preparation subacute toxicity]. Farmakolohiia ta likarska toksykolohiia. 2022;16(4):248-63. Ukrainian. doi: https://doi.org/10.33250/16.04.248

Knysh Y, Panasenko O, Safonov A, inventors. [Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate, which shows actoprotective activity]. Ukrainian patent UA 112619. 2016 Sep 26. Available from: https://sis.nipo.gov.ua/en/search/detail/455441/

Guide for the Care and Use of Laboratory Animals [Internet]. Washington, D.C.: National Academies Press; 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54050/

European Union. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union, L276/33, 2010.

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Published

2024-06-14

How to Cite

1.
Safonov AA, Panasenko OI, Al Khalaf NA. Study of the effect of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)- 4H-1,2,4-triazole-3-yl)thio)acetate toxic doses on rats heart tissue. Current issues in pharmacy and medicine: science and practice [Internet]. 2024Jun.14 [cited 2024Oct.24];17(2):150-3. Available from: http://pharmed.zsmu.edu.ua/article/view/300859