Assessment of the hepatotoxic potential of organot in compounds containing 2,6-di-tert-butylphenol fragme


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The article is devoted to the in vivo study of the effect of organotin compounds containing 2,6-di-tert-butylphenol fragment on liver mor- pho-functional state. The aim of this study was to evaluate the biochemical and histological changes in the liver with a single intragastric administration of bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Me3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenyltin (Me5) to Wistar rats (female) at the maximum tolerated dose (MTD) of 2000 mg/kg and 750 mg/kg, respectively. It was found that the introduction of Me3 and Me5 do not cause significant structural changes in liver, and the disorders are of a functional nature. The results of this work allow us to conclude that the hepatotoxicity of organotin compounds containing 2,6-di-tert-butylphenol is low, which opens up broad prospects for studying these compounds as candidates for antitumor drugs

Full Text

Restricted Access

About the authors

M. A Dodokhova

Rostov State Medical University

Email: dodohova@mail.ru
Ph.D. (Med.), Associate Professor, Department of Biomedicine and Neuroscience, and General and Clinical Biochemistry No. 2

A. V Safronenko

Rostov State Medical University

Email: andrejsaf@mail.ru
Dr.Sc. (Med.), Professor, Department of Pharmacology and Clinical Pharmacology

I. M Kotieva

Rostov State Medical University

Email: kukulik70@mail.ru
Dr.Sc. (Med.), Professor, Department of Pathological Physiology

E. R Milaeva

Lomonosov Moscow State University

Email: milaeva@med.chem.msu.ru
Dr.Sc. (Chem.), Professor, Department of Medicinal Chemistry and Fine Organic Synthesis

D. B Shpakovsky

Lomonosov Moscow State University

Email: dmshpak@mail.ru
Ph.D. (Chem.), Senior Researcher, Department of Medicinal Chemistry and Fine Organic Synthesis

Yu. M Makarenko

Pathologic and Anatomical Bureau of the Russian Academy of Sciences

Email: markovich1962@yandex.ru
Ph.D. (Med.)

V. G Trepel

Federal State Budgetary Institution "IMCEUAOSMP" of Roszdravnadzor

Email: vartantrepel.61@gmail.com
Ph.D. (Med.), Rostov-on-Don branch

M. S Alkhuseyn-Kulyaginova

Rostov State Medical University

Email: rita.kuljaginva@rambler.ru
Senior Laboratory Assistant, Department of Chemistry

References

  1. Состояние онкологической помощи населению России в 2019 году / Под ред. А.Д. Каприна, В.В. Старинского, А. О. Шахзадовой. М.: МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИЦ радиологии» Минздрава России. 2020; 239 с.
  2. Azad A., Chang P., Deepika D., et al. Real world experience of drug induced liver injury in patients undergoing chemotherapy. J. Clin. Gastroenterol. Hepatol. 2018; 2(3):18.
  3. Полунина Т.Е., Маев И.В. Лекарственный гепатит. Consilium medicum. Гастроэнтерология. 2008; 1:3-10.
  4. Ивашкин В.Т., Барановский А.Ю., Райхельсон К.Л. и др. Лекарственные поражения печени (клинические рекомендации для врачей). Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2019; 29(1 ):101-131.
  5. Banti C.N., Hadjikakou S.K., Sismanoglu T., Hadjiliadis N. Anti-proliferative and antitumor activity of organotin (IV) compounds. An overview of the last decade and future perspectives. J. Inorg. Biochem. 2019; 194:114-152.
  6. Shpakovsky D.B., Banti C.N., Mukhatova E.M. et al. Synthesis, antiradical activity and in vitro cytotoxicity of novel organotin complexes based on 2,6-di-tert-butyl-4-mercaptophenol. Dalton Trans. 2014; 43:6880-6890.
  7. OECD Guideline for testing of chemicals. Acute Oral Toxicity -Fixed Dose Procedure No. 420. OECD Publishing, Paris, 2001.
  8. OECD, Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure. OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, 2008. https://doi.org/10.1787/9789264071049-en
  9. Коптяева К.Е., Мужикян А.А., Гущин Я.А. и др. Методика вскрытия и извлечения органов лабораторных животных (крысы). Лабораторные животные для научных исследований. 2018; 2:71-92.
  10. Хабриев Р. У. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ. М.: Медицина, 2005; 832 с.
  11. Aithal G.P., Watkins P.B., Andrade R.J., et al. Review. Case definition and phenotype standardization in drug-induced liver injury. Clin. Pharmacol. Ther. 2011; 89(6):806-815.
  12. Milaeva E.R., Tyurin V.Y., Gracheva Y.A. et al. Protective Effect of Meso-Tetrakis-(3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin on the In Vivo Impact of Trimethyltin Chloride on the Antioxida-tive Defense System. Bioinorg. Chem. Appl. 2006; 2006:64927.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2021 Russkiy Vrach Publishing House

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies