Serum Molecular Fingerprints of Oxidative Stress Underlying Neurocognitive and Motor Dysfunction in Pesticide-Exposed...

We investigated the relationship between chronic pesticide exposure, oxidative stress, and neurocognitive alterations in rural populations of Celendín, Cajamarca, Peru. A total of 101 adults (18-86 years) were evaluated through neuropsychological (NEUROPSI) and neuromotor assessments, serum oxidative stress biomarkers, and Fourier-transform infrared spectroscopy (FT-IR) of serum samples. Biomarkers analyzed included superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), total glutathione, lipid peroxidation (malondialdehyde), biopyrrins (BPn), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Statistical comparisons (Mann-Whitney U) and multivariate analyses (PCA, PLS-DA) were performed to identify biochemical and spectral alterations. Pesticide users exhibited a significantly higher frequency of attention deficit (OR = 4.4, 95% CI = 1.2-15.9) and elevated serum 8-OHdG levels (p = 0.042), indicating increased oxidative DNA damage. While antioxidant enzyme activities did not differ significantly, higher malondialdehyde and BPn levels suggested enhanced lipid and bilirubin oxidation. FT-IR analysis revealed distinct spectral signatures in individuals with moderate cognitive impairment, impaired left-hand motor control, and executive dysfunction (calculation). Significant bands appeared in the 440-493 cm^-1 region (disulfide/polysulfide bonds), 2573 cm^-1 (thiols), and 3630-3840 cm^-1 (free hydroxyl groups), consistent with oxidative protein and glycan modifications. Additional signals between 2089 and 2255 cm^-1 suggested carbamylation-related isothiocyanate and cyanate groups. These findings suggest that oxidative stress is a key mechanism underlying pesticide-related neurocognitive dysfunction. Combining oxidative stress biomarkers with FT-IR provides a rapid, minimally invasive approach for identifying serum molecular fingerprints with potential applications in screening and monitoring pesticide-induced neurotoxicity.