Umbelliferone reverses neuronal damage induced by chronic Chlorpyrifos exposure via suppressing NF-κB/STAT3/NLRP3 and boosting Keap-1/Nrf2/HO-1 signals.

Abstract

Chlorpyrifos (CPF), an organophosphate pesticide, is a widely used pest control chemical. Unfortunately, pesticides are known to cause neuronal intoxication. Umbelliferone (UMB) is an antioxidant, anti-inflammatory, and neuroprotective phytochemical. We plan to investigate the effectiveness of UMB in treating CPF-induced neurotoxicity. In our investigation, rats were assigned to the control, 30 mg/kg of UMB, 10 mg/kg of untreated CPF, CPF + UMB (15 mg/kg), and CPF + UMB (30 mg/kg) groups. UMB reduced neuronal intoxication by lowering p-Tau/Tau and β-amyloid. UMB reduced CPF-induced neuronal oxidative damage by lowering MDA content and increasing GSH levels, mediated by downregulating Keap1 and upregulating Nrf2, HO-1, and SOD3. UMB decreased CPF-induced brain inflammation by lowering TNF-α and IL-6 levels by suppressing NF-κB and STAT3 activation and downregulating NLRP3 dose-dependently. Our findings indicated that UMB is a potentially effective treatment approach for reducing CPF-induced neuronal intoxication by restoring the balance between oxidants and antioxidants and reducing inflammatory responses in brain tissues.