Cytoprotective effect of alpha-2-macroglobulin against pesticide-induced generation of ROS in neuronal SH-SY5Y cells

Introduction: Many clinical studies have demonstrated that continuous exposure to pesticides, especially organophosphates and pyrethroids, causes toxicities such as carcinogenicity and neu-rotoxicity that lead to disorders such as diabetes, lung cancer, and neurodegenerative diseases. The mechanism underlying pesticide-induced neurotoxicity involves the production of ROS, which causes neuronal injury through oxidative stress. Methods: In the present study, the neuronal SH-SY5Y cell line was used to investigate the effect of the pesticides chlorpyrifos (organophosphate), aldicarb (carbamate), and deltamethrin (pyrethroid) on ROS-mediated toxicity and the protective effect of alpha-2-macroglobulin (a2M), a protease inhibitor and beta-amyloid plaque scavenger in the human brain. For cell viability and cytotoxicity, the MTT assay was performed. To moni-tor ROS production, assays such as DCFHDA, H2O2, and MDA were performed, along with assays of the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. Results: The experimental findings suggest a cytoprotective role for a2M in ROS-mediated toxic-ity that causes neuronal injury in humans. Conclusion: Hence, a2M could be possibly used as a protective agent against oxidative neurotoxicity caused by pesticides.