Tetra aniline-based polymers ameliorate BPA-induced cardiotoxicity in Sprague Dawley rats, in silico and in vivo analysis.

Autor: Ishtiaq A; Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, 45320, Pakistan., Mushtaq I; Department of Chemistry, Quaid-i-Azam University Islamabad, Pakistan., Rehman H; Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, 45320, Pakistan., Mushtaq I; Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, 45320, Pakistan., Mushtaq I; Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, 45320, Pakistan., Abbasi SW; Department of Biological Sciences, National University of Medical Sciences, 46000 Rawalpindi, Pakistan., Liaqat F; Department of Chemistry, Quaid-i-Azam University Islamabad, Pakistan., Rasheed A; Department of Chemistry, Quaid-i-Azam University Islamabad, Pakistan., Ahmad S; Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan., Akhtar Z; Department of Chemistry, Quaid-i-Azam University Islamabad, Pakistan., Murtaza I; Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, 45320, Pakistan. Electronic address: irambch@qau.edu.pk.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Dec 01; Vol. 358, pp. 123104. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1016/j.lfs.2024.123104
Abstrakt: Aims: Bisphenol A (BPA), xenoestrogen, is an environmental toxicant, that generates oxidative stress leading to cardiotoxicity. The oxidative stress can be neutralized by natural and synthetic antioxidants. The present study elucidates the highly selective antioxidative potential of synthetic tetra aniline polymers Es-37 and L-37 against Bisphenol A-induced cardiac cellular impairments and the role of miRNA-15a-5p in the regulation of different apoptotic proteins.
Materials and Methods: The molecular docking of L-37 and Es-37 with three proteins (p53, Cytochrome c, and Bcl-2) were performed. The dose of 1 mg/kg BW of BPA, 1 mg/kg BW Es-37 and L-37 and 50 mg/kg BW N-acetyl cysteine (NAC) was administered to Sprague Dawley rats. The miRNA and target gene expression were confirmed by qRt-PCR and Immunoblotting.
Key Findings: In our results, BPA administration significantly elevated the reactive oxygen species (ROS), p53, cytochrome c, and particularly miRNA-15a-5p expression; however: these changes were notably reversed by Es-37 and L-37 treatment. Additionally, molecular docking of synthetic polymers validated that L-37 has a greater binding affinity with the target proteins compared to Es-37, with the highest binding values reported for the enzymatic protein cytochrome c.
Significance: These results suggest that both synthetic polymers Es-37 and L-37 have the potential to scavenge free radicals, boost-up antioxidant enzyme activities, and avert (BPA-induced) toxicity, thus, may serve as cardioprotective agents. Moreover, this study first time proposes that miRNA-15a-5p overexpression is associated with oxidative stress and coincides with BPA induced cardiotoxicity, thus may serve as potential therapeutic target in future.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Iram Murtaza reports administrative support and equipment, drugs, or supplies were provided by Higher Education Commission Pakistan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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