Перегляд за Автор "Bendas, S. I."

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    In silico study of the anti-inflammatory properties of PFOA, PFOS, KClO4, and AlCl3
    (Одеський національний університет імені І. І. Мечникова, 2024) Bendas, S. I.; Galkin, Borys M.; Kyrylenko, Natalia A.; Бендас, С. І.; Галкін, Борис Миколайович; Кириленко, Наталя Анатоліївна
    Introduction. Military operations cause great damage to the environment. The great-est environmental threat in this situation is chemical pollution (carbon oxides, nitro-gen oxides, formaldehyde, hydrogen cyanide, potassium perchlorate, aluminum and various toxic organic substances). In addition, ammunition may contain per- and polyfluoroalkyl substances (PFAS), which are characterized by exceptional envi-ronmental stability. Among the most famous PFAS are perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), which exhibit exceptional stability and resistance to degradation. In our opinion, these chemical compounds are highly toxic and can enhance inflammatory processes in the body. Aim. to study the potential toxicity of perfluorooctanoic acid, perfluorooctane sulfonic acid, AlCl₃ and KClO4 using in silico approaches. Methods. The toxicity of aluminum chloride, potassium perchlorate, perfluorooctanoic acid, and perfluorooctane sulfonic acid was calculated using the ProTox 3.0 virtual laboratory based on machine learning algorithms. Molecular docking was performed using AutoDock Vina 1.2.5. (http://vina.scripps.edu), Schrödinger Maestro–2023–2 Glide (trial license). The molecular docking procedure was performed using the crystal structure of human serum albumin (7Z57), crystal structures of the ligand-binding domain of human PPAR-gamma (2F4B), human monoamine oxidase A in complex with clorgyline (2BXR), human COX-1 Crystal Structure (6Y3C) from the PDB database of biological macromolecules (http://www.rcsb.org/). During the studies, docking of perfluorooctanoic acid and perfluorooctane sulfonic acid was performed. Molecular dynamics simulations were performed for the complex (perfluorooctanoic acid – human serum albumin, AlCl3 – human serum albumin) using the PlayMolecule software. Results. Based on the ProTox 3.0 virtual laboratory based on machine learning for toxicity prediction, all compounds (KClO4, AlCl3, perfluorooctanoic acid, perfluorooctanoic sulfonic acid) show significant toxicity potential through several pathways such as carcinogenicity, nephrotoxicity for perfluorooctanoic acid, respiratory toxicity for perfluorooctanoic sulfonic acid, cardiotoxicity for AlCl3 and estrogen receptor alpha toxicity for KClO4. According to ProTox 3.0, perfluorooctanoic acid and perfluorooctanoic sulfonic acid can interact with prostaglandin G/H synthase 1 and amine oxidase A. Human serum albumin showed the best docking score and binding free energy among the target proteins when docked with perfluorooctanoic acid and perfluorooctanoic sulfonic acid. The molecular docking results indicate that PFOS has moderate binding affinities with Monoamine Oxidase A and COX-1. These results are theoretical predictions and require further experimental studies. Conclusions. Toxicity studies using the ProTox 3.0 virtual laboratory and molecular docking revealed significant toxicological potential of the compounds tested (KClO₄, AlCl₃, perfluorooctanoic acid, perfluorooctanoic acid). Binding of PFOA to human serum albumin, resulting in its stabilization, may disrupt many of the essential functions that HSA performs in the blood. This binding may promote bioaccumulation, interfere with normal transport processes, affect drug efficacy, and potentially lead to chronic health problems due to ongoing exposure to PFAS toxicity. Thus, the persistence of PFOA-bound HSA in the circulation may be a pathway for long-term exposure and associated health risks.