Cerium oxide nanoparticles alleviate pesticide-induced cholinergic dysfunction in the rat hippocampus

Abstract

Objective: This research explored the neuroprotective potential of cerium oxide nanoparticles (CeO₂ NPs) against chlorpyrifos (CPF)-induced cholinergic dysfunction in the rat hippocampus, assessing acetylcholinesterase (AChE) and muscarinic M1 receptor (CHRM1) gene expression, plus oxidative stress markers.

Methods: Forty adult male Wistar rats were randomly assigned to four groups (n=10): control (vehicle), CPF-only (5 mg/kg/day oral gavage), CeO₂ NPs-only (0.5 mg/kg/day intraperitoneal), and CPF + CeO₂ NPs (co-treatment for 28 days). Hippocampal AChE and CHRM1 expression were quantified by qRT-PCR. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured via commercial kits.

Results: CPF reduced AChE and CHRM1 mRNA levels by 42% and 31% vs. controls (p < 0.001), with elevated lipid peroxidation (MDA: 356 ± 42 vs. 98 ± 11 nmol/mg protein; p < 0.001) and reduced antioxidant enzymes (SOD: −43%; CAT: −43%; GPx: −45%). CeO₂ NPs co-treatment significantly attenuated these effects, restoring AChE and CHRM1 expression to 76% and 71% of control (p < 0.01 vs. CPF-only). MDA decreased by 48% (p < 0.001), and antioxidant enzyme activities recovered by 74–87% (p < 0.01). CeO₂ NPs alone caused no adverse effects.

Conclusions: CeO₂ nanoparticles effectively attenuate CPF-induced hippocampal cholinergic dysfunction by preserving cholinergic gene expression and redox homeostasis. These findings support CeO₂ NPs as a promising approach for treating organophosphate neurotoxicity.