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Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate

β-thalassemia is one of the most common monogenic disorders and a life-threatening health issue in children. A cost-effective and safe therapeutic approach to treat this disease is to reactivate the γ-globin gene for fetal hemoglobin (HbF) production that has been silenced during infancy. Hydroxyure...

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Autores principales: Kumari, Sindhia, Khan, Faisal, Siddiqui, Amna Jabbar, Adil, Nurmeen, Uddin, Jalal, Asmari, Mufarreh, Musharraf, Syed Ghulam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778960/
https://www.ncbi.nlm.nih.gov/pubmed/36555396
http://dx.doi.org/10.3390/ijms232415750
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author Kumari, Sindhia
Khan, Faisal
Siddiqui, Amna Jabbar
Adil, Nurmeen
Uddin, Jalal
Asmari, Mufarreh
Musharraf, Syed Ghulam
author_facet Kumari, Sindhia
Khan, Faisal
Siddiqui, Amna Jabbar
Adil, Nurmeen
Uddin, Jalal
Asmari, Mufarreh
Musharraf, Syed Ghulam
author_sort Kumari, Sindhia
collection PubMed
description β-thalassemia is one of the most common monogenic disorders and a life-threatening health issue in children. A cost-effective and safe therapeutic approach to treat this disease is to reactivate the γ-globin gene for fetal hemoglobin (HbF) production that has been silenced during infancy. Hydroxyurea (HU) is the only FDA approved HbF inducer. However, its cytotoxicity and inability to respond significantly in all patients pose a need for an HbF inducer with better efficacy. The study describes the serum metabolic alteration in β-YAC transgenic mice treated with Tenofovir disoproxil fumarate (TDF) (n = 5), a newly identified HbF inducer, and compared to the mice groups treated with HU (n = 5) and untreated control (n = 5) using gas chromatography-mass spectrometry. Various univariate and multivariate statistical analyses were performed to identify discriminant metabolites that altered the biological pathways encompassing galactose metabolism, lactose degradation, and inositol. Furthermore, the decreased concentrations of L-fucose and geraniol in TDF-treated mice help in recovering towards normal, decreasing oxidative stress even much better than the HU-treated mice. The proposed study suggested that TDF can reduce the deficiency of blood required for β-thalassemia and can be used for the preclinical study at phase I/II for fetal hemoglobin production.
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spelling pubmed-97789602022-12-23 Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate Kumari, Sindhia Khan, Faisal Siddiqui, Amna Jabbar Adil, Nurmeen Uddin, Jalal Asmari, Mufarreh Musharraf, Syed Ghulam Int J Mol Sci Article β-thalassemia is one of the most common monogenic disorders and a life-threatening health issue in children. A cost-effective and safe therapeutic approach to treat this disease is to reactivate the γ-globin gene for fetal hemoglobin (HbF) production that has been silenced during infancy. Hydroxyurea (HU) is the only FDA approved HbF inducer. However, its cytotoxicity and inability to respond significantly in all patients pose a need for an HbF inducer with better efficacy. The study describes the serum metabolic alteration in β-YAC transgenic mice treated with Tenofovir disoproxil fumarate (TDF) (n = 5), a newly identified HbF inducer, and compared to the mice groups treated with HU (n = 5) and untreated control (n = 5) using gas chromatography-mass spectrometry. Various univariate and multivariate statistical analyses were performed to identify discriminant metabolites that altered the biological pathways encompassing galactose metabolism, lactose degradation, and inositol. Furthermore, the decreased concentrations of L-fucose and geraniol in TDF-treated mice help in recovering towards normal, decreasing oxidative stress even much better than the HU-treated mice. The proposed study suggested that TDF can reduce the deficiency of blood required for β-thalassemia and can be used for the preclinical study at phase I/II for fetal hemoglobin production. MDPI 2022-12-12 /pmc/articles/PMC9778960/ /pubmed/36555396 http://dx.doi.org/10.3390/ijms232415750 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kumari, Sindhia
Khan, Faisal
Siddiqui, Amna Jabbar
Adil, Nurmeen
Uddin, Jalal
Asmari, Mufarreh
Musharraf, Syed Ghulam
Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate
title Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate
title_full Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate
title_fullStr Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate
title_full_unstemmed Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate
title_short Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate
title_sort metabolomics study of serum samples of β-yac transgenic mice treated with tenofovir disoproxil fumarate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778960/
https://www.ncbi.nlm.nih.gov/pubmed/36555396
http://dx.doi.org/10.3390/ijms232415750
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