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Nano-pelargonidin modulates p53/PARP/HSP 90/XRCC1 signaling axis to combat cypermethrin-induced genotoxicity and metabolic dysfunction in fish: a molecular docking predicted in vivo approach
Environmental Science: Nano ( IF 7.3 ) Pub Date : 2024-03-19 , DOI: 10.1039/d3en00965c
Priyanka Sow 1 , Sudatta Dey 1 , Rishita Dey 1, 2 , Asmita Samadder 1 , Sisir Nandi 2 , Debojyoti Tarafdar 3 , Anisur Rahman Khuda-Bukhsh 1
Affiliation  

Pesticides and other products used in agricultural practices often find their way into nearby waterbodies through agricultural run-offs, contributing to pollution and affecting non-target organisms, especially edible fish, posing a risk to human health. In this study, an attempt is made to address this global issue by formulating a possible nano-phyto-product that can combat the genotoxic and metabolic effects of pesticides in fish models. Thus, poly-lactide-co-glycolide (PLGA)-encapsulated nano-pelargonidin (NPG) was synthesized and characterized via AFM, FESEM, DLS, and CD methods. An in silico molecular docking study was conducted to identify the signalling proteins that interact with the phyto-core-compound pelargonidin (PG) to predict the effectiveness of NPG in combating pesticide-induced toxicity. Thereafter, the predicted signalling proteins, p53, PARP, and HSP 90, were tracked in Oreochromis mossambicus to investigate the possible effect of NPG in combating cypermethrin (CM)-induced genotoxicity-associated dysfunctions, such as ROS generation, alteration in MMP, micronucleus formation, and histopathological changes. Overall, the results revealed that pre-treatment with negatively charged PLGA-encapsulated NPG (∼64 nm) showed protective efficacy against CM-induced genotoxicity by modulating the activity of biological macromolecules such as DNA-repair proteins and stress proteins, which was corroborated by molecular docking predictions. Thus, the present strategy appears to be a cost-effective method for combating pesticide-induced toxicity issues quite effectively to restore environmental harmony and protect non-target organisms, like fish.

中文翻译:

纳米天竺葵素调节 p53/PARP/HSP 90/XRCC1 信号轴以对抗氯氰菊酯诱导的鱼类遗传毒性和代谢功能障碍:体内预测的分子对接方法

农业实践中使用的农药和其他产品经常通过农业径流进入附近水体,造成污染并影响非目标生物,特别是食用鱼类,对人类健康构成风险。在这项研究中,试图通过配制一种可能的纳米植物产品来解决这一全球性问题,该产品可以对抗农药对鱼类模型的遗传毒性和代谢影响。因此,通过AFM、FESEM、DLS 和 CD 方法合成并表征了聚丙交酯-共-乙交酯 (PLGA) 封装的纳米天竺葵素 (NPG) 进行了一项计算机分子对接研究,以确定与植物核心化合物天竺葵素 (PG) 相互作用的信号蛋白,以预测 NPG 在对抗农药引起的毒性方面的有效性。此后,在Oreochromis mossambicus中追踪预测的信号蛋白 p53、PARP 和 HSP 90,以研究 NPG 在对抗氯氰菊酯 (CM) 诱导的遗传毒性相关功能障碍(如 ROS 生成、MMP 改变、微核)方面的可能作用。形成和组织病理学变化。总体而言,结果表明,用带负电的 PLGA 封装的 NPG(~64 nm)进行预处理,通过调节 DNA 修复蛋白和应激蛋白等生物大分子的活性,显示出对 CM 诱导的遗传毒性的保护作用,这一点得到了证实分子对接预测。因此,本策略似乎是一种具有成本效益的方法,可以非常有效地对抗农药引起的毒性问题,以恢复环境和谐并保护非目标生物(如鱼类)。
更新日期:2024-03-20
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