Therapeutic Effects of Fucoidan in 6‐Hydroxydopamine‐Lesioned Rat Model of Parkinson's disease: Role of NADPH oxidase‐1

摘要

Summary Aims To explore the effect of fucoidan treatment on oxidative stress‐mediated dopaminergic neuronal damage and its potential mechanisms. Methods The effect of fucoidan was investigated in a 6‐hydroxydopamine (6‐OHDA) rat model of PD, an animal model considered appropriate for preclinical studies of PD therapy. The effects of fucoidan treatment on animal behavior and the survival ratio of dopaminergic neurons were investigated. We further observed the effect of fucoidan on microglia and the NADPH oxidases‐1 (Nox1), a family of enzymes generating reactive oxygen species ( ROS ). Results We found that chronic fucoidan administration mitigated the motor dysfunction induced by 6‐ OHDA . Similarly, fucoidan reduced the loss of DA neurons in the SN c and DA fibers in the striatum in 6‐ OHDA ‐lesioned rats. Moreover, we found that fucoidan inhibited the 6‐ OHDA ‐stimulating expression of Nox1 in both tyrosine hydroxylase ( TH )‐positive neurons and non‐ TH ‐positive neurons, prevented Nox1‐sensitive oxidative stress and cell damage in SN c neurons. Fucoidan also effectively inhibited nigral microglial activation. Conclusion These results support the beneficial effect of fucoidan in 6‐ OHDA ‐lesioned rat model of PD . Fucoidan may suppress the Nox1‐triggered oxidative stress in the SN c to protect DA neurons from 6‐ OHDA ‐induced toxicity and achieve its beneficial effect.