Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assay

Rifampicin, isoniazid, ethambutol, pyrazinamide, and/or their fixed-dose combination (FDC) are the first-line tuberculosis (TB) antibiotics used as a 6-month regimen. We evaluated the cytogenotoxic effects of these drugs using the murine micronucleus assay. Male Swiss albino mice were int...

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Main Authors: Adekunle A. Bakare, Charles T. Beckley, Obi M. Ebelechukwu, Adeyinka M. Gbadebo, Motunrayo M. Coker, Omonike C. Bakare, Olukunle S. Fagbenro, Okunola A. Alabi
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Language:English
Published: Academia.edu Journals 2025-01-01
Series:Academia Biology
Online Access:https://www.academia.edu/127362846/Somatic_cytogenotoxicity_of_first_line_anti_tuberculosis_drugs_using_the_mouse_micronucleus_assay
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author Adekunle A. Bakare
Charles T. Beckley
Obi M. Ebelechukwu
Adeyinka M. Gbadebo
Motunrayo M. Coker
Omonike C. Bakare
Olukunle S. Fagbenro
Okunola A. Alabi
author_facet Adekunle A. Bakare
Charles T. Beckley
Obi M. Ebelechukwu
Adeyinka M. Gbadebo
Motunrayo M. Coker
Omonike C. Bakare
Olukunle S. Fagbenro
Okunola A. Alabi
author_sort Adekunle A. Bakare
collection DOAJ
description Rifampicin, isoniazid, ethambutol, pyrazinamide, and/or their fixed-dose combination (FDC) are the first-line tuberculosis (TB) antibiotics used as a 6-month regimen. We evaluated the cytogenotoxic effects of these drugs using the murine micronucleus assay. Male Swiss albino mice were intraperitoneally exposed for 5 consecutive days to 1.25, 2.50, 5.00, 10.00, and 20.00 mg/kg bw of rifampicin; 0.63, 1.25, 2.50, 5.00, and 10.00 mg/kg bw of isoniazid; 1.88, 3.75, 7.50, 15.00, and 30.00 mg/kg bw of ethambutol; 3.13, 6.25, 12.50, 25.00, and 50.00 mg/kg bw of pyrazinamide; and 3.50, 7.00, 14.00, 28.00, and 56.00 mg/kg bw of FDC. Normal saline and cyclophosphamide (20 mg/kg bw) were used as negative and positive controls, respectively. At the tested doses, the drugs induced a dose-independent increase in micronucleated polychromatic erythrocyte (MNPCE) and micronucleated normochromatic erythrocyte (MNNCE) compared with the negative control. The induction was statistically significant at most of the tested doses of the drugs. There was a significant increase in the percentage PCE:NCE ratio in the bone marrow cells of mice at the tested doses of isoniazid, pyrazinamide, and the FDC. These results indicate that the individual anti-TB drug and their FDC possess DNA-damaging potential in the somatic cells of mice.
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spelling doaj-art-66a8e427089a4f96a72d2749941cdda52025-08-20T02:09:28ZengAcademia.edu JournalsAcademia Biology2837-40102025-01-013110.20935/AcadBiol7503Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assayAdekunle A. Bakare0Charles T. Beckley1Obi M. Ebelechukwu2Adeyinka M. Gbadebo3Motunrayo M. Coker4Omonike C. Bakare5Olukunle S. Fagbenro6Okunola A. Alabi7Department of Zoology, Cell Biology and Genetics Unit, University of Ibadan, Ibadan, Oyo State 200005, Nigeria.Department of Zoology, Cell Biology and Genetics Unit, University of Ibadan, Ibadan, Oyo State 200005, Nigeria.Department of Zoology, Cell Biology and Genetics Unit, University of Ibadan, Ibadan, Oyo State 200005, Nigeria.Department of Molecular Biology and Biotechnology, Chrisland University, Owode, Abeokuta, Ogun State 23409, Nigeria.Department of Zoology, Cell Biology and Genetics Unit, University of Ibadan, Ibadan, Oyo State 200005, Nigeria.Department of Biological Sciences, Lead City University, Ibadan, Oyo State 200255, Nigeria.Department of Zoology, Cell Biology and Genetics Unit, University of Ibadan, Ibadan, Oyo State 200005, Nigeria.Department of Biology, Federal University of Technology, Akure, Ondo State 340001, Nigeria. Rifampicin, isoniazid, ethambutol, pyrazinamide, and/or their fixed-dose combination (FDC) are the first-line tuberculosis (TB) antibiotics used as a 6-month regimen. We evaluated the cytogenotoxic effects of these drugs using the murine micronucleus assay. Male Swiss albino mice were intraperitoneally exposed for 5 consecutive days to 1.25, 2.50, 5.00, 10.00, and 20.00 mg/kg bw of rifampicin; 0.63, 1.25, 2.50, 5.00, and 10.00 mg/kg bw of isoniazid; 1.88, 3.75, 7.50, 15.00, and 30.00 mg/kg bw of ethambutol; 3.13, 6.25, 12.50, 25.00, and 50.00 mg/kg bw of pyrazinamide; and 3.50, 7.00, 14.00, 28.00, and 56.00 mg/kg bw of FDC. Normal saline and cyclophosphamide (20 mg/kg bw) were used as negative and positive controls, respectively. At the tested doses, the drugs induced a dose-independent increase in micronucleated polychromatic erythrocyte (MNPCE) and micronucleated normochromatic erythrocyte (MNNCE) compared with the negative control. The induction was statistically significant at most of the tested doses of the drugs. There was a significant increase in the percentage PCE:NCE ratio in the bone marrow cells of mice at the tested doses of isoniazid, pyrazinamide, and the FDC. These results indicate that the individual anti-TB drug and their FDC possess DNA-damaging potential in the somatic cells of mice.https://www.academia.edu/127362846/Somatic_cytogenotoxicity_of_first_line_anti_tuberculosis_drugs_using_the_mouse_micronucleus_assay
spellingShingle Adekunle A. Bakare
Charles T. Beckley
Obi M. Ebelechukwu
Adeyinka M. Gbadebo
Motunrayo M. Coker
Omonike C. Bakare
Olukunle S. Fagbenro
Okunola A. Alabi
Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assay
Academia Biology
title Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assay
title_full Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assay
title_fullStr Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assay
title_full_unstemmed Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assay
title_short Somatic cytogenotoxicity of first-line anti-tuberculosis drugs using the mouse micronucleus assay
title_sort somatic cytogenotoxicity of first line anti tuberculosis drugs using the mouse micronucleus assay
url https://www.academia.edu/127362846/Somatic_cytogenotoxicity_of_first_line_anti_tuberculosis_drugs_using_the_mouse_micronucleus_assay
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