Nano-therapeutics in Combating Pesticide Infestation in Edible Fish and Mammalian Cell Lines via Selectively Activating the p53/PARP Signalling Axis and Focusing on the Gut Microbiome
Arnob Chakrovorty, Banani Bhattacharjee, Sayoni Dam, Sisir Nandi, Debojyoti Tarafdar, Asmita SamadderIntroduction:
Pesticide poisoning has grown to be a global threat that requires urgent attention. Human consumption of aquatic animals exposed to pesticide wash-off has become a serious concern, as water bodies carrying pesticides from surrounding agricultural fields become harmful for non-target insects and other organisms of the same or other ecological niches. Fish that are stressed by this pesticide- induced toxicity have lower nutritional value and are therefore less suitable for safe consumption.
Methods:
This study aims to counter the toxicological effects imparted by the pyrethroid insecticide Cypermethrin (CM) in the Oreochromis mossambicus fish model and in the L6 mammalian skeletal cell line by the administration of Poly-Lactide-co-Glycolide (PLGA) encapsulated chlorophyllin nanoparticles (NCHL).
Results:
SEM characterization revealed that the NCHL was 60 nm in size, with a smooth surface topology devoid of cracks or crevices and a uniform spatial frequency, with a zeta potential of -12.3 mV. NCHL pre-treatment reduced CM-induced stress by modulating vital physiological parameters, such as total protein content and the percentage viability of muscle, liver, and kidney cells, and by reducing cellular ROS via modulation of key enzymes, including Superoxide Dismutase (SOD), Catalase (CAT), and Lipid Peroxidase (LPO), in vivo. Additionally, ELISA and confocal fluorescence microscopy validated that NCHL could modulate the expression of DNA repair proteins, PARP (in vivo) and p53 (in vitro and in vivo), as a means to counter CM-induced genotoxic effects.
Discussion:
Nano-encapsulation showed greater effectiveness owing to its nano-scale size, which aided in better and faster permeation and a greater amount of compound for crossing the cellular membrane and enhancing uptake at the cellular level, thereby modulating the cascade of proteins in a targeted way to regulate, or rather inhibit, the extent of toxicity that would be imparted by the pesticide in the living system.
Conclusion:
The PLGA-encapsulated nano formulation approach would definitely pave the way for a better livelihood for humanity and reduce the risk of consuming pesticide-contaminated fish or other aquatic organisms in the times to come.