Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypes

The objective: in the experiment, to study specific parameters of manifestations of hepatotoxic reactions to the combination of anti-tuberculosis drugs containing isoniazid and rifampicin in rats with different acetylation phenotypes. Subjects and methods. Liver damage was modeled in rats, old femal...

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Main Authors: G. N. Mozhokina, А. V. Kazakov, Yu. R. Zyuzya, L. Yu. Petrova
Format: Article
Language:Russian
Published: New Terra Publishing House 2020-08-01
Series:Туберкулез и болезни лёгких
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Online Access:https://www.tibl-journal.com/jour/article/view/1444
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author G. N. Mozhokina
А. V. Kazakov
Yu. R. Zyuzya
L. Yu. Petrova
author_facet G. N. Mozhokina
А. V. Kazakov
Yu. R. Zyuzya
L. Yu. Petrova
author_sort G. N. Mozhokina
collection DOAJ
description The objective: in the experiment, to study specific parameters of manifestations of hepatotoxic reactions to the combination of anti-tuberculosis drugs containing isoniazid and rifampicin in rats with different acetylation phenotypes. Subjects and methods. Liver damage was modeled in rats, old females, belonging to the phenotype of rapid acetylation, and in mature males, belonging to the phenotype of slow acetylation, with a combination of basic anti-tuberculosis drugs, which were administered for 14 days. Hepatotoxic reactions were assessed by clinical observations of rats, biochemical parameters and morphological changes in the liver, which were compared with intact animals. Results of the study: in female rats (fast acetylators of isoniazid), signs of the cytolytic mechanism of liver damage prevailed (more significant elevation of ALT activity, pronounced duration of thiopental sleep, pronounced hydropic degeneration of hepatocytes with the presence of hepatocyte necrosis, venous congestion and edema of the portal tracts). In males (with the phenotype of slow acetylation of isoniazid), a significant elevation of total and direct bilirubin levels, AST activity and, to a lesser extent, ALT were observed, i.e., signs of a mixed mechanism of liver damage (cholestatic and cytolytic).
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issn 2075-1230
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publishDate 2020-08-01
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record_format Article
series Туберкулез и болезни лёгких
spelling doaj-art-1a0148cd16f844f7b5dc26a992499a5c2025-08-20T02:16:01ZrusNew Terra Publishing HouseТуберкулез и болезни лёгких2075-12302542-15062020-08-01987515510.21292/2075-1230-2020-98-7-51-551443Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypesG. N. Mozhokina0А. V. Kazakov1Yu. R. Zyuzya2L. Yu. Petrova3National Medical Research Center of Phthisiopulmonology and Infectious DiseasesNational Medical Research Center of Phthisiopulmonology and Infectious DiseasesNational Medical Research Center of Phthisiopulmonology and Infectious DiseasesNational Medical Research Center of Phthisiopulmonology and Infectious DiseasesThe objective: in the experiment, to study specific parameters of manifestations of hepatotoxic reactions to the combination of anti-tuberculosis drugs containing isoniazid and rifampicin in rats with different acetylation phenotypes. Subjects and methods. Liver damage was modeled in rats, old females, belonging to the phenotype of rapid acetylation, and in mature males, belonging to the phenotype of slow acetylation, with a combination of basic anti-tuberculosis drugs, which were administered for 14 days. Hepatotoxic reactions were assessed by clinical observations of rats, biochemical parameters and morphological changes in the liver, which were compared with intact animals. Results of the study: in female rats (fast acetylators of isoniazid), signs of the cytolytic mechanism of liver damage prevailed (more significant elevation of ALT activity, pronounced duration of thiopental sleep, pronounced hydropic degeneration of hepatocytes with the presence of hepatocyte necrosis, venous congestion and edema of the portal tracts). In males (with the phenotype of slow acetylation of isoniazid), a significant elevation of total and direct bilirubin levels, AST activity and, to a lesser extent, ALT were observed, i.e., signs of a mixed mechanism of liver damage (cholestatic and cytolytic).https://www.tibl-journal.com/jour/article/view/1444anti-tuberculosis drugsacetylation phenotypeshepatotoxic reactionsexperimentrats
spellingShingle G. N. Mozhokina
А. V. Kazakov
Yu. R. Zyuzya
L. Yu. Petrova
Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypes
Туберкулез и болезни лёгких
anti-tuberculosis drugs
acetylation phenotypes
hepatotoxic reactions
experiment
rats
title Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypes
title_full Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypes
title_fullStr Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypes
title_full_unstemmed Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypes
title_short Parameters of hepatotoxic reactions caused by the combination of first line anti-tuberculosis drugs in rats with different acetylation phenotypes
title_sort parameters of hepatotoxic reactions caused by the combination of first line anti tuberculosis drugs in rats with different acetylation phenotypes
topic anti-tuberculosis drugs
acetylation phenotypes
hepatotoxic reactions
experiment
rats
url https://www.tibl-journal.com/jour/article/view/1444
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AT avkazakov parametersofhepatotoxicreactionscausedbythecombinationoffirstlineantituberculosisdrugsinratswithdifferentacetylationphenotypes
AT yurzyuzya parametersofhepatotoxicreactionscausedbythecombinationoffirstlineantituberculosisdrugsinratswithdifferentacetylationphenotypes
AT lyupetrova parametersofhepatotoxicreactionscausedbythecombinationoffirstlineantituberculosisdrugsinratswithdifferentacetylationphenotypes