Nano-pelargonidin modulates p53/PARP/HSP 90/XRCC1 signaling axis to combat cypermethrin-induced genotoxicity and metabolic dysfunction in fish: a molecular docking predicted approach

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. Nano-pelargonidin protects CM-induced toxicity in tilapia fish by modulating DNA repair proteins corroborating with molecular docking study.