Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety Profiles

The objective: to evaluate the variety of adverse reactions to combinations of clofazimine with anti-tuberculosis and antimicrobial drugs with different and similar toxic profiles.Subjects and Methods: Studies were carried on non-pedigree female rats at the age of 10-11 months. In Group 1, rats rece...

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Main Authors: G. N. Mozhokina, Yu. R. Zyuzya, L. Yu. Petrova, A. G. Samoylova
Format: Article
Language:Russian
Published: New Terra Publishing House 2022-11-01
Series:Туберкулез и болезни лёгких
Subjects:
Online Access:https://www.tibl-journal.com/jour/article/view/1680
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author G. N. Mozhokina
Yu. R. Zyuzya
L. Yu. Petrova
A. G. Samoylova
author_facet G. N. Mozhokina
Yu. R. Zyuzya
L. Yu. Petrova
A. G. Samoylova
author_sort G. N. Mozhokina
collection DOAJ
description The objective: to evaluate the variety of adverse reactions to combinations of clofazimine with anti-tuberculosis and antimicrobial drugs with different and similar toxic profiles.Subjects and Methods: Studies were carried on non-pedigree female rats at the age of 10-11 months. In Group 1, rats received Cfz + Bdq + Mxf + Clr, in Group 2 – Cfz + Bdq + Lzd + Z daily for 14 days. A comprehensive examination upon completion of drug administration included functional (ECG, behavioral reactions), laboratory and pathomorphological assessments.Results. The combination of Cfz + Bdq + Mxf + Clr had a pronounced cardiotoxicity: it caused QT prolongation up to 0.053 ± 0.002 s and individual fluctuations within ranges up to 20 ms; some rats demonstrated qualitative ECG changes. Hepatotoxic reactions were revealed according to laboratory and morphological parameters, and morphological signs of mild kidney dystrophy were found in most rats. Neurotoxic reactions were manifested as a decrease in motor and exploratory activities. The combination of Cfz + Bdq + Lzd + Z did not cause significant ECG changes; mild signs of hepatotoxicity and nephrotoxicity were observed in single rats, behavioral disorders manifested only as emotional depression of the animals. Significant differences in the variety and degree of adverse reactions are due to the combination of clofazimine with drugs possessing similar cardiotoxic potential – bedaquiline, moxifloxacin, and clarithromycin.
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spelling doaj.art-feb12b977a1a45df8c9f1f4fa7b814612023-09-03T10:32:28ZrusNew Terra Publishing HouseТуберкулез и болезни лёгких2075-12302542-15062022-11-0110010152110.21292/2075-1230-2022-100-10-15-211675Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety ProfilesG. N. Mozhokina0Yu. R. Zyuzya1L. Yu. Petrova2A. G. Samoylova3ФГБУ «Национальный медицинский исследовательский центр фтизиопульмонологии и инфекционных заболеваний» МЗ РФФГБУ «Национальный медицинский исследовательский центр фтизиопульмонологии и инфекционных заболеваний» МЗ РФФГБУ «Национальный медицинский исследовательский центр фтизиопульмонологии и инфекционных заболеваний» МЗ РФФГБУ «Национальный медицинский исследовательский центр фтизиопульмонологии и инфекционных заболеваний» МЗ РФThe objective: to evaluate the variety of adverse reactions to combinations of clofazimine with anti-tuberculosis and antimicrobial drugs with different and similar toxic profiles.Subjects and Methods: Studies were carried on non-pedigree female rats at the age of 10-11 months. In Group 1, rats received Cfz + Bdq + Mxf + Clr, in Group 2 – Cfz + Bdq + Lzd + Z daily for 14 days. A comprehensive examination upon completion of drug administration included functional (ECG, behavioral reactions), laboratory and pathomorphological assessments.Results. The combination of Cfz + Bdq + Mxf + Clr had a pronounced cardiotoxicity: it caused QT prolongation up to 0.053 ± 0.002 s and individual fluctuations within ranges up to 20 ms; some rats demonstrated qualitative ECG changes. Hepatotoxic reactions were revealed according to laboratory and morphological parameters, and morphological signs of mild kidney dystrophy were found in most rats. Neurotoxic reactions were manifested as a decrease in motor and exploratory activities. The combination of Cfz + Bdq + Lzd + Z did not cause significant ECG changes; mild signs of hepatotoxicity and nephrotoxicity were observed in single rats, behavioral disorders manifested only as emotional depression of the animals. Significant differences in the variety and degree of adverse reactions are due to the combination of clofazimine with drugs possessing similar cardiotoxic potential – bedaquiline, moxifloxacin, and clarithromycin.https://www.tibl-journal.com/jour/article/view/1680противотуберкулезные препаратыантимикробные препаратыклофазиминнежелательные реакцииэксперимент
spellingShingle G. N. Mozhokina
Yu. R. Zyuzya
L. Yu. Petrova
A. G. Samoylova
Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety Profiles
Туберкулез и болезни лёгких
противотуберкулезные препараты
антимикробные препараты
клофазимин
нежелательные реакции
эксперимент
title Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety Profiles
title_full Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety Profiles
title_fullStr Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety Profiles
title_full_unstemmed Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety Profiles
title_short Variety of Adverse Reactions in Rats after Administration of Combination of Anti-tuberculosis and Antimicrobial Drugs with Different Safety Profiles
title_sort variety of adverse reactions in rats after administration of combination of anti tuberculosis and antimicrobial drugs with different safety profiles
topic противотуберкулезные препараты
антимикробные препараты
клофазимин
нежелательные реакции
эксперимент
url https://www.tibl-journal.com/jour/article/view/1680
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AT lyupetrova varietyofadversereactionsinratsafteradministrationofcombinationofantituberculosisandantimicrobialdrugswithdifferentsafetyprofiles
AT agsamoylova varietyofadversereactionsinratsafteradministrationofcombinationofantituberculosisandantimicrobialdrugswithdifferentsafetyprofiles