Effects of anti-parkinsonian drugs on the production of dopamine o-quinone (DAQ) in an in-vitro brain slice model
-
1
Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary
Parkinson’s disease (PD) is a neurodegenerative syndrome associated with selective loss of neuromelanin-containing dopaminergic neurons in the striatum. Among the proposed mechanisms of dopaminergic degeneration, oxidative stress is believed to play an important role. Neuromelanin formation is the outcome of a process generally known as dopamine (DA) autooxidation, a chain of oxidation reactions in which highly neurotoxic DA-quinones are produced. Development of an effective causal therapy should be focused on preventing or at least retarding the neurodegenerative process underlying the disease. In this study we examined the effects of anti-parkinsonian drugs l-DOPA, l-deprenyl, rasagiline, bromocriptine and the antioxidant trolox on rotenone pre-treated rat striatum. Striatal slices from 190-205 g male Wistar rats were perfused with Krebs solution using the microvolume perfusion method and neurochemical changes in the collected samples were followed by HPLC analysis. The analytical system included two-dimensional, reversed-phase ion pair gradient liquid chromatographic separation and multi-dimensional (electrochemical, UV and liquid scintillation) detection techniques to measure the changes induced by different drugs. Dopamine o-quinone (DAQ), the oxidized metabolite of DA was detected electrochemically at -100 mV potential in reduction working mode. Formation of DAQ (6.92±0.5 % n=4) at the end effect of oxidative stress induced by H2O2 indicated the impairment of dopaminergic function by rotenone. When rotenone was applied with l-DOPA treatment, endogenous DAQ was again detected in the micro-volume perfusion samples. Conversely, when rasagiline and trolox were in use these DA-quinones metabolites were not detectable. The results obtained demonstrate that the direct detection of DA-quinone used in this work is useful and provide new insights into the neurochemical changes occurring in response to anti-Parkinsonian drug effect.
Conference:
12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009.
Presentation Type:
Poster Presentation
Topic:
Pathophysiology and neurology - degenerative disorders
Citation:
Baranyi
M,
Milusheva
E and
Sperlágh
B
(2009). Effects of anti-parkinsonian drugs on the production of dopamine o-quinone (DAQ) in an in-vitro brain slice model.
Front. Syst. Neurosci.
Conference Abstract:
12th Meeting of the Hungarian Neuroscience Society.
doi: 10.3389/conf.neuro.01.2009.04.138
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
04 Mar 2009;
Published Online:
04 Mar 2009.
*
Correspondence:
Maria Baranyi, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary, baranyi@koki.hu