Mariano_2026_Basic.Clin.Pharmacol.Toxicol_139_e70288

Chlorpyrifos (CP) is an organophosphate insecticide that induces neurotoxicity through acetylcholinesterase (AChE) inhibition and redox imbalance, raising environmental and occupational health concerns. Plant-derived compounds from Senecio brasiliensis, native to the Pampa biome, offer multitarget therapeutic potential. This study evaluated the protective effects of the hydroalcoholic extract of S. brasiliensis (HESB) against CP-induced toxicity in Drosophila melanogaster (Harwich strain). Adult females (3-5 days old) were exposed for 48 h to control (1% sucrose), CP (0.25 ppm), HESB (1 mg/mL) or CP + HESB. CP increased mortality (37.3% +/- 6.6%; p < 0.001) and impaired locomotion in the negative geotaxis (17.2 +/- 3.0 s; p < 0.001) and footbridge (52.2 +/- 5.2 s) assays, decreased AChE, GST and CAT activity (-31.8%, -45.8% and -72.3%, respectively; p = 0.006, 0.025 and 0.006), elevated ROS (+97.0%; p = 0.007), nitrite (+13.1%; p = 0.006) and TBARS (+25.6%; p = 0.010), depleted NPSH (-29.2%; p = 0.003) and PSH (-35.9%; p = 0.013) and reduced cell viability (-17.9%; p = 0.013). HESB co-treatment attenuated all CP-induced alterations, bringing parameters to control-comparable values (p > 0.05). These findings indicate that HESB exerts neuroprotective effects against CP toxicity through modulation of cholinergic function, attenuation of oxidative and nitrosative stress and preservation of thiol homeostasis.