Neuroprotective effect of diosmin against chlorpyrifos-induced brain intoxication was mediated by regulating PPAR-γ...

Chlorpyrifos (CPF) is a widely used organophosphate (OP) pesticide. Unfortunately, pesticides are known to cause neuronal intoxication. Diosmin (DS) is an antioxidant, anti-inflammatory, and neuroprotective flavonoid with high efficacy and safety. We plan to investigate the efficacy of DS in treating CPF-induced neurotoxicity, as well as the mechanisms underlying the protective effects. In our study, rats were randomized into 5 groups: control, DS (50 mg/kg), CPF (10 mg/kg), CPF + DS (25 mg/kg), and CPF + DS (50 mg/kg). The results indicated that DS ameliorated neuronal intoxication induced by CPF, evidenced by decreasing Tau, p-Tau, and β-amyloid. Histological examinations support these findings. DS significantly ameliorated CPF-induced neuronal oxidative injury by decreasing MDA content and elevating GSH, GST, and SOD levels mediated by PPAR-γ upregulation. DS suppressed CPF-induced brain inflammation by decreasing MPO enzymatic activity and TNF-α, IL-1β, and IL-6 levels mediated by downregulation of NF-κB/AP-1(c-FOS and c-JUN) signal. Of note, DS protective effects were dose dependent. In conclusion, our data suggested that DS was a promising therapeutic strategy for attenuating CPF-induced neuronal intoxication by restoring oxidant-antioxidant balance and inhibiting inflammatory response in brain tissues.