Comparative efficacy of ethylmethylhydroxypyridine succinate derivatives in acute CCl4 intoxication

G.A. Plisko, Junior Researcher, Center for Experimental Pharmacology, https://orcid.org/0000-0003-0869-3430

U.V. Nogaeva, postgraduate student of the 1st year of origin, junior researcher, https://orcid.org/0000-0002-8214-7553

E.D. Semivelichenko, Junior Researcher, Center for Experimental Pharmacology .: https://orcid.org/0000-0002-8464-7711

D.Y. Ivkin, Cand. biol. Sci., Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Head of the Center for Experimental Pharmacology,: https://orcid.org/0000-0001-9273-6864

I.A. Titovich, Cand. biol. Sciences, Director of the Department of Science and Training of Scientific and Pedagogical Personnel, https://orcid.org/0000-0002-1343-4663

E.V. Flisyuk, professor, head. Department of Technology of Dosage Forms, Vice-Rector for Research https://orcid.org/0000-0001-8077-2462

N.V. Demakova, Junior Researcher, Center for Experimental Pharmacology https://orcid.org/0000-0002-2145-9289

A.S. Ivkina, Researcher, Center for Experimental Pharmacology: https://orcid.org/0000-0002-4938-1321


Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State Chemical-Pharmaceutical University" of the Ministry of Health of Russia, Center for Experimental Pharmacology (CEP),

Head of CEP, Ph.D., Associate Professor of the Department of Pharmacology and Clinical Pharmacology Ivkin Dmitry Yurievich,

197022, St. Petersburg, st. Professor Popov 4/6

Е-mail: grigoriy.plisko@pharminnotech.com

 

Abstract

Tetrachloromethane is actively used to simulate pathologies of the liver, as well as other organs, due to its acute toxic effect, leading to systemic endotoxicosis. Ethylmethylhydroxypyridine (EMHPS) succinate is an antioxidant and antihypoxant, and in a number of studies hepatotropic activity has been shown. The metabolite of this compound, namely ethylmethylsulfoperidine (EMSP), has also shown a positive effect on various liver parameters in some studies. In this connection, it was decided to simulate acute intoxication, using intraperitoneal injection of carbon tetrachloride, to assess the effectiveness of these substances. For this, equimolar doses of both substances and a seven-day model of acute poisoning were calculated. The present study was carried out on 40 male rats, randomizing them into 4 groups. Tetrachloromethane is a classic toxin for simulating liver damage due to the formation of highly reactive radicals, which are the product of biotransformation by cytochrome P-450. Our research has shown that intraperitoneal administration of carbon tetrachloride in oily solution is an effective way to simulate liver damage. At the end of the experiment, blood was taken from the animals for biochemical and hematological analysis. After autopsy, the liver was isolated for histological examination. Alanine aminotransferase and aspartate aminotransferase levels were elevated during biochemical analysis, consistent with similar studies. In the group of the study drug, the levels of alanine aminotransferase and aspartate aminotrasferase were lower than in the group of the reference drug, which indicates a positive effect of EMSP on the biochemical parameters of the liver, as well as an effective counteraction of the toxic agent. The cholesterol level in the study group did not significantly differ from the comparison drug group, but the difference was from the pathology group, which confirms the effective effect of EMSP in acute carbon tetrachloride poisoning. The blood count by hematological analysis also showed an improvement in the group receiving the test substance. The histological results of the study showed that the development of centrilobular cholestasis in the pаtology group and the group receiving succinate together with carbon tetrachloride and emethylhydroxypyridine was approximately at the same level, which indicates the insufficient effectiveness of EMHPS in acute intoxication. The same indicator in the group receiving both carbon tetrachloride and ethylmethylsulfopyridine was lower, as well as fatty degeneration, the severity of which was less in the group of the study drug than in the groups of potassium and EMHPS. Histological analysis also showed that fine droplet degeneration was less pronounced in the group of the test substance. Based on the totality of the estimated indicators, it can be assumed that ethylmethylsulfopyridine in the model of acute intoxication with carbon tetrachloride was more effective than the reference drug ethylmethylhydroxypyridine succinate.

Full text avaliable in Russain only 

Autors’ contributions

Plisko G.A. – research idea, work performance, data collection from literary sources, writing the text of the article.

Ivkin D.Yu. – Editing the article

Nogaeva U.V. – statistical data processing

Flisyuk E.V. – writing the text of the article

Titovich I.A. – analysis of literature data

Semivelichenko E.D. – participation in the experiment

Demakova N.V. – participation in the experiment, animal care

Ivkina A.S. – processing of primary data

Conflict of interest

The authors declare no conflict of interest.
 

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