Doxycycline and its derivative, COL-3, decrease dyskinesia induced by l-DOPA in hemiparkinsonian rats.
Animals
Antiparkinson Agents
Corpus Striatum
Disease Models, Animal
Doxycycline
Dyskinesia, Drug-Induced
/ drug therapy
Levodopa
Male
Matrix Metalloproteinase 2
Matrix Metalloproteinase 3
Matrix Metalloproteinase 9
Oxidopamine
Rats
Rats, Sprague-Dawley
Rats, Wistar
Reactive Oxygen Species
Tetracyclines
Parkinson's disease
ROS
astrocytes
inflammation
metalloproteinase
microglia
neuroinflammation
striatum
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
03
12
2020
received:
17
06
2020
accepted:
16
02
2021
pubmed:
23
3
2021
medline:
6
7
2021
entrez:
22
3
2021
Statut:
ppublish
Résumé
l-DOPA-induced dyskinesia is a debilitating effect of treating Parkinson's disease with this drug. New therapeutic approaches that prevent or attenuate this side effect are needed. Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesion were treated with l-DOPA (p.o. 20 mg·kg A single injection of doxycycline or COL-3 attenuated l-DOPA-induced dyskinesia. Co-treatment with doxycycline from the first day of l-DOPA suppressed the onset of dyskinesia. The improved motor response after l-DOPA was not affected by doxycycline or COL-3. Doxycycline treatment was associated with decreased immunoreactivity of FosB, COX-2, the astroglial protein GFAP and the microglial protein OX-42, which were elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline decreased metalloproteinase-2/-9 activity, metalloproteinase-3 expression and ROS production. Metalloproteinase-2/-9 activity and production of ROS in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia. The present study demonstrates the anti-dyskinetic potential of doxycycline and its analogue compound COL-3 in hemiparkinsonian rats. Given the long-established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or prevent l-DOPA-induced dyskinesia in Parkinson's patients.
Sections du résumé
BACKGROUND AND PURPOSE
l-DOPA-induced dyskinesia is a debilitating effect of treating Parkinson's disease with this drug. New therapeutic approaches that prevent or attenuate this side effect are needed.
EXPERIMENTAL APPROACH
Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesion were treated with l-DOPA (p.o. 20 mg·kg
KEY RESULTS
A single injection of doxycycline or COL-3 attenuated l-DOPA-induced dyskinesia. Co-treatment with doxycycline from the first day of l-DOPA suppressed the onset of dyskinesia. The improved motor response after l-DOPA was not affected by doxycycline or COL-3. Doxycycline treatment was associated with decreased immunoreactivity of FosB, COX-2, the astroglial protein GFAP and the microglial protein OX-42, which were elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline decreased metalloproteinase-2/-9 activity, metalloproteinase-3 expression and ROS production. Metalloproteinase-2/-9 activity and production of ROS in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia.
CONCLUSION AND IMPLICATIONS
The present study demonstrates the anti-dyskinetic potential of doxycycline and its analogue compound COL-3 in hemiparkinsonian rats. Given the long-established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or prevent l-DOPA-induced dyskinesia in Parkinson's patients.
Substances chimiques
Antiparkinson Agents
0
Reactive Oxygen Species
0
Tetracyclines
0
tetracycline CMT-3
0
Levodopa
46627O600J
Oxidopamine
8HW4YBZ748
Matrix Metalloproteinase 3
EC 3.4.24.17
Matrix Metalloproteinase 2
EC 3.4.24.24
Matrix Metalloproteinase 9
EC 3.4.24.35
Doxycycline
N12000U13O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2595-2616Informations de copyright
© 2021 The British Pharmacological Society.
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