Serum Molecular Fingerprints of Oxidative Stress Underlying Neurocognitive and Motor Dysfunction in Pesticide‐Exposed Populations

ABSTRACT 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.