Permethrin pesticide residues in food mediate progressive neuronal disorder

Objective: Pyrethroids are used in many formulations in agriculture to control insect pests in crops, forestry and horticulture. Environmental exposure results from dietary intake and this is confirmed by the quantification in human urine of the 3-PBA pyrethroid metabolite. The exposure to xenobiotics in the early stages of life, represents the most important component in the etiology of neurodegenerative diseases (1-3). Here, the impact of permethrin administered to rats from 6th to 21st day of life, was studied in adult animals by proteomic analysis of plasma and striatum. The concentration of permethrin and its 3-PBA metabolite were also evaluated. Methods: GC-MS/SIM and GC-ECD were used to detect 3-PBA and permethrin in urine and striatum samples of rats 24 h and 14 days after the treatment. Two-dimensional electrophoresis followed by LC-MS/MS analysis was used for proteomic analysis. Results: Permethrin in the brain was found at either 24 h or 14 days after the end of treatment and it was 10 times higher at 14 days; while the 3-PBA levels was higher at 24 h in both brain and urine. In plasma, long chain fatty acid protein transporter resulted significantly decreased on treated animal compared to control group. In striatum, mitochondrial Aspartate aminotransferase and voltage dependent anion channel were down expressed while Malate dehydrogenase, Myelin basic protein and Ubiquitin-60S ribosomal protein L40 resulted completely absent. Conclusion: Permethrin accumulation in striatum can be responsible for the long term effects reported in striatum leading to down expression of proteins associated with neuronal disorder. Proteomic data can be utilized as biomarkers of neurodegeneration. References: 1. Carloni, M., Nasuti, C., Fedeli, D., Montani, M., Amici, A., Vadhana, M.S., Gabbianelli, R., 2012. The impact of early life permethrin exposure on development of neurodegeneration in adulthood, Exp Gerontol. 47, 60-66. 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. Fedeli, D., Montani, M., Nasuti, C., Gabbianelli, R., 2014. Early life permethrin treatment induces in striatum of older rats changes in alpha-synuclein content, Journal Nutrigenetics and Nutrigenomics 7, 80.