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Article

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

by
Sindhia Kumari
1,
Faisal Khan
2,
Amna Jabbar Siddiqui
2,
Nurmeen Adil
1,
Jalal Uddin
3,
Mufarreh Asmari
3 and
Syed Ghulam Musharraf
1,2,4,*
1
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
2
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
3
Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 61421, Asir, Saudi Arabia
4
The Affiliated T.C.M Hospital of Southwest Medical University, Luzhou 646099, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(24), 15750; https://doi.org/10.3390/ijms232415750
Submission received: 6 August 2022 / Revised: 12 September 2022 / Accepted: 15 September 2022 / Published: 12 December 2022
(This article belongs to the Section Molecular Pharmacology)
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Abstract

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.
Keywords: tenofovir disoproxil fumarate; β-thalassemia; β-YAC transgenic mice; fetal hemoglobin induction; pharmacometabolomics; GC-MS tenofovir disoproxil fumarate; β-thalassemia; β-YAC transgenic mice; fetal hemoglobin induction; pharmacometabolomics; GC-MS
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MDPI and ACS Style

Kumari, S.; Khan, F.; Siddiqui, A.J.; Adil, N.; Uddin, J.; Asmari, M.; Musharraf, S.G. Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate. Int. J. Mol. Sci. 2022, 23, 15750. https://doi.org/10.3390/ijms232415750

AMA Style

Kumari S, Khan F, Siddiqui AJ, Adil N, Uddin J, Asmari M, Musharraf SG. Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate. International Journal of Molecular Sciences. 2022; 23(24):15750. https://doi.org/10.3390/ijms232415750

Chicago/Turabian Style

Kumari, Sindhia, Faisal Khan, Amna Jabbar Siddiqui, Nurmeen Adil, Jalal Uddin, Mufarreh Asmari, and Syed Ghulam Musharraf. 2022. "Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate" International Journal of Molecular Sciences 23, no. 24: 15750. https://doi.org/10.3390/ijms232415750

APA Style

Kumari, S., Khan, F., Siddiqui, A. J., Adil, N., Uddin, J., Asmari, M., & Musharraf, S. G. (2022). Metabolomics Study of Serum Samples of β-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate. International Journal of Molecular Sciences, 23(24), 15750. https://doi.org/10.3390/ijms232415750

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