Protective effect of glutathione on damage induced by permethrin in a neuronal model of PC12 cells.

Objective: Permethrin, a member of the family of synthetic pyrethroids, can induce oxidative stress and impairment in expression of Nurr1, a transcription factor essential for the maintenance of dopaminergic neurons. These conditions, flanked to low level of glutathione (GSH), are typical in neurons affected by Parkinson Disease (PD). The aim of this study is to evaluate in vitro effects of GSH on a stress dependent parameters (Nurr1) measured in PC12 cells culture treated with permethrin. Methods: PC12 cells were seeded and treated for 72h with 1uM permethrin and separately co-treated with the pesticide and 32nM glutathione (1). Then, qRT-PCR was performed to evaluate Nurr1 gene expression. Results: In cells cultures under stress condition, such as those induced by permethrin, Nurr1 gene expression changed, maybe as a compensatory effect to damage. In contrast, when cells were co-treated with glutathione, Nurr1 value was reestablished as the control. Conclusion: Pesticides, mainly assumed with diet, can modulate gene expression leading to the onset and progression of age-related diseases. Permethrin, in particular, can induce stress in neuronal dopaminergic cells, mimicking PD condition (2). As demonstrated by previous in vivo studies, permethrin exposure can lead to progressive neuronal damage characterized by GSH and Nurr1 deficit (3,4). The present study shows that GSH in vitro can contrast the negative effect induced by permethrin. We can hypothesize that GSH can prevent oxidative stress damage, avoiding cells to overreact by modifying the production of Nurr1. Hence, GSH can act as a preventive agent to cellular damage induced by permethrin. References 1. Mesner PW, Winters TR, Green SH. (1992). Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons. J Cell Biol 119:1669–1680. 2. Carloni, M., Nasuti, C., Fedeli, D., Montani. M., Amici, A., Vadhana, M.S.D., Gabbianelli, R., 2013. Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2, Brain Research 1515, 19-28. 3. Falcioni ML, Nasuti C, Bergamini C, Fato R, Lenaz G. ( 2010). The primary role of GSH against nuclear DNA damage of striatum induced by permethrin in rats. Neuroscience 168(1), 2-10. 4. Nasuti C, Falcioni ML, Nwankwo IE, Cantalamessa F, Gabbianelli R. (2008). Effect of permethrin plus antioxidants on locomotor activity and striatum in adolescent rats. Toxicology., 29;251(1-3):45-50.