NDLI: Oral Treatment with the NADPH Oxidase Antagonist Apocynin Mitigates Clinical and Pathological Features of Parkinsonism in the MPTP marmoset Model

Content Provider	Springer Nature Link
Author	Philippens, Ingrid H. C. H. M. Wubben, Jacqueline A. Finsen, Bente Hart, Bert A.
Copyright Year	2013
Abstract	This study evaluates the therapeutic efficacy of the NADPH oxidase inhibitor apocynin, isolated as principal bioactive component from the medicinal plant Picrorhiza kurroa, in a marmoset MPTP model of Parkinson’s disease (PD). The methoxy-substituted catechol apocynin has a similar structure as homovanillic acid (HVA), a metabolite of dopamine (DA). Apocynin acquires its selective inhibitory capacity of the reactive oxygen species generating NADPH oxidase via metabolic activation by myeloperoxidase (MPO). As MPO is upregulated in activated brain microglia cells of PD patients and in MPTP animal models, the conditions for metabolic activation of apocynin and inhibition of microglia NADPH oxidase are in place. Marmoset monkeys received oral apocynin (100 mg/kg; p.o.) (n = 5) or Gum Arabica (controls; n = 5) three times daily until the end of the study, starting 1 week before PD induction with MPTP (1 mg/kg s.c. for 8 days). Parkinsonian symptoms, motor function, home-cage activity and body weight were monitored to assess the disease development and severity. Post-mortem numbers of the tyrosine hydroxylase expressing DA neurons in the substantia nigra were counted. During the MPTP injections, apocynin limited the body weight loss and relieved parkinsonian symptoms compared to controls (Linear regression, P < 0.05) indicating a reduction of disease progression. During the last test week, apocynin also improved the hand-eye coordination performance compared with vehicle treatment (resp. 39.3 ± 4.5 % and 17.7 ± 6.7 %; P = 0.048) and improved the home cage activity with 32 % (P = 0.029), indicating anti-Parkinson efficacy. Apocynin also increased the number of surviving DA neurons in MPTP-treated marmosets with 8.5 % (P = 0.059), indicating a tendency towards a neuroprotective efficacy. In conclusion, compensation for the loss of DA and its metabolite HVA by apocynin mitigates the PD progression and limits the parkinsonian signs and motor-function deterioration.
Starting Page	715
Ending Page	726
Page Count	12
File Format	PDF
ISSN	15571890
Journal	Journal of Neuroimmune Pharmacology
Volume Number	8
Issue Number	3
e-ISSN	15571904
Language	English
Publisher	Springer US
Publisher Date	2013-03-17
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Behavior Catechol Marmoset monkey Microglia Parkinson’s disease MPTP Neurosciences Immunology Pharmacology/Toxicology Virology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Allergy Pharmacology Immunology

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