Therapeutic effects of fucoidan in 6-hydroxydopamine-lesioned rat model of Parkinson's disease: Role of NADPH oxidase-1.
OBJECTIVE
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 SNc 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 SNc neurons. Fucoidan also effectively inhibited nigral microglial activation.


CONCLUSIONS
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 SNc to protect DA neurons from 6-OHDA-induced toxicity and achieve its beneficial effect.
Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, China; Beijing Institute for Brain Disorders, Beijing, China.
Fei-Long
FL
Zhang
Yi
Y
He
Yan
Y
Zheng
Wen-Jing
WJ
Zhang
Qi
Q
Wang
Yan-Jun
YJ
Jia
Hai-Long
HL
Song
Hai-Ting
HT
An
Hao-Bo
HB
Zhang
Yan-Jing
YJ
Qian
Yu-Long
YL
Tong
Lin
L
Dong
Xiao-Min
XM
Wang
D018663:Adrenergic Agents / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology; D011134:Polysaccharides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D039481:CD11b Antigen; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D016627:Oxidopamine; C007789:fucoidan; D014446:Tyrosine 3-Monooxygenase; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat
6-OHDA; Fucoidan; NADPH oxidase-1; Oxidative stress; Substantia nigra