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The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice

Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on t...

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Autores principales: Bakare, Adekunle A., Moses, Victoria Y., Beckely, Charles T., Oluyemi, Toluwani I., Ogunfeitimi, Gift O., Adelaja, Aduragbemi A., Ayorinde, Glory T., Gbadebo, Adeyinka M., Fagbenro, Olukunle S., Ogunsuyi, Olusegun I., Ogunsuyi, Opeoluwa M., Ige, Olusoji Mayowa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793334/
https://www.ncbi.nlm.nih.gov/pubmed/36582470
http://dx.doi.org/10.3389/fcell.2022.1023413
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author Bakare, Adekunle A.
Moses, Victoria Y.
Beckely, Charles T.
Oluyemi, Toluwani I.
Ogunfeitimi, Gift O.
Adelaja, Aduragbemi A.
Ayorinde, Glory T.
Gbadebo, Adeyinka M.
Fagbenro, Olukunle S.
Ogunsuyi, Olusegun I.
Ogunsuyi, Opeoluwa M.
Ige, Olusoji Mayowa
author_facet Bakare, Adekunle A.
Moses, Victoria Y.
Beckely, Charles T.
Oluyemi, Toluwani I.
Ogunfeitimi, Gift O.
Adelaja, Aduragbemi A.
Ayorinde, Glory T.
Gbadebo, Adeyinka M.
Fagbenro, Olukunle S.
Ogunsuyi, Olusegun I.
Ogunsuyi, Opeoluwa M.
Ige, Olusoji Mayowa
author_sort Bakare, Adekunle A.
collection PubMed
description Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11–13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice.
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spelling pubmed-97933342022-12-28 The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice Bakare, Adekunle A. Moses, Victoria Y. Beckely, Charles T. Oluyemi, Toluwani I. Ogunfeitimi, Gift O. Adelaja, Aduragbemi A. Ayorinde, Glory T. Gbadebo, Adeyinka M. Fagbenro, Olukunle S. Ogunsuyi, Olusegun I. Ogunsuyi, Opeoluwa M. Ige, Olusoji Mayowa Front Cell Dev Biol Cell and Developmental Biology Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11–13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice. Frontiers Media S.A. 2022-12-13 /pmc/articles/PMC9793334/ /pubmed/36582470 http://dx.doi.org/10.3389/fcell.2022.1023413 Text en Copyright © 2022 Bakare, Moses, Beckely, Oluyemi, Ogunfeitimi, Adelaja, Ayorinde, Gbadebo, Fagbenro, Ogunsuyi, Ogunsuyi and Ige. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Bakare, Adekunle A.
Moses, Victoria Y.
Beckely, Charles T.
Oluyemi, Toluwani I.
Ogunfeitimi, Gift O.
Adelaja, Aduragbemi A.
Ayorinde, Glory T.
Gbadebo, Adeyinka M.
Fagbenro, Olukunle S.
Ogunsuyi, Olusegun I.
Ogunsuyi, Opeoluwa M.
Ige, Olusoji Mayowa
The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice
title The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice
title_full The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice
title_fullStr The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice
title_full_unstemmed The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice
title_short The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice
title_sort first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793334/
https://www.ncbi.nlm.nih.gov/pubmed/36582470
http://dx.doi.org/10.3389/fcell.2022.1023413
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