Exposure to low dose of pesticide in early life modifies the plasma protein profile in adolescent rats

Objectives The neonatal period is an important phase of life in which environmental factors (i.e. xenobiotics, nutrition) and hormonal, metabolic and neural disorders may influence gene expression with the development of diseases in adulthood. Our previous studies underlined the correlation between early life environmental exposure to xenobiotics and the development of long-time toxic effects; we have demonstrated that the treatment of rats from 6th to 21st day of life with low dose of pesticide permethrin induced in adult age neurodegeneration especially on dopaminergic system (Carloni et al. 2012; Carloni et al., 2013). Recently we studied the effect of early life permethrin treatment at peripheral level (Vadhana et al., 2011; Fedeli et al. 2012) and we observed in leukocytes an increased Nurr1 protein level in the treated group in old age with respect to its control together with an impairment of GSH and lipid peroxidation in plasma. The objective of this study was to screen all plasma proteins in order to identify early plasma biomarkers useful to intervene with therapeutic approaches in the first phase of the disease. Methods Male Wistar rat pups were administered once a day with permethrin (34.05 mg/kg) from PND6 to PND21. Plasma of adolescent rats ( 90 days old) from control and treated groups was collected and analyzed by a two-dimensional gel electrophoresis (2-DE) followed by a liquid chromatography- tandem mass spectrometry (LC-MS/MS) to sequence protein spots of interest. Results We identified four differently expressed spots in permethrin-treated samples with respect to control specimens: transthyretin (TTR), serum transferrin (2 isoforms) and long chain fatty acid transport protein. TTR and serum transferin levels were significantly lower in serum of permethrin-treated rats with respect to controls (not treated rats). In particular, we identified two isoforms of serum transferrin, a small one (isoform 2) with a measured molecular weight of 55.7 kDa and a biggest one (isoforms 1) with a measured molecular weight of 86.0 kDa, The isoform 2 was present only in the serum of control rats whereas the isoform 1 was present in the serum of permethrin-treated rats but in lowest amount with respect to controls. In addition, the long chain fatty acid transport 1 protein was completely absent in the serum of permethrin-treated rats while it was abundant in control rats serum. Conclusions The decreased presence of TTR and transferrin in serum of treated rats should be considered as biomarkers indicating the early stage of the neurodegenerative disease.