{"title":"Tetra aniline-based polymers ameliorate BPA-induced cardiotoxicity in Sprague Dawley rats, in silico and in vivo analysis.","authors":"Ayesha Ishtiaq, Irrum Mushtaq, Hina Rehman, Iqra Mushtaq, Iram Mushtaq, Sumra Wajid Abbasi, Faroha Liaqat, Ammarah Rasheed, Sajjad Ahmad, Zareen Akhtar, Iram Murtaza","doi":"10.1016/j.lfs.2024.123104","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Key findings: </strong>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 averted and 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.</p><p><strong>Significance: </strong>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.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.lfs.2024.123104","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
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 averted and 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.
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.