Impairment of neuronal mitochondrial function by l-DOPA in the absence of oxygen-dependent auto-oxidation and oxidative cell damage

Hörmann, Philipp; Delcambre, Sylvie; Hanke, Jasmin E.; Geffers, Robert; Leist, Marcel; Hiller, Karsten

doi:10.1038/s41420-021-00547-4

Cited by 14 publications

(11 citation statements)

References 82 publications

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“…Recent studies have also shown that even oxygen tension affects LD stability. Under normoxic conditions, the analyte is prone to auto-oxidation by releasing protons and reactive oxygen species (ROS) as intermediates [ 33 , 34 ]. In acidic conditions, protons supplied by solvents would shift the auto-oxidation reaction equilibrium towards the reagents and avoid the formation of intermolecular bonding networks [ 30 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…Firstly, LD is unstable in aqueous solutions and naturally degrades over time [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]: for this reason, it is crucial to identify the best conditions to avoid LD degradation over all the analytical steps. LD instability will also influence the choice of the extraction technique.…”

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a Reversed-Phase HPLC Method with UV Detection for the Determination of L-Dopa in Vicia faba L. Broad Beans

et al. 2022

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L-Dopa (LD), a substance used medically in the treatment of Parkinson’s disease, is found in several natural products, such as Vicia faba L., also known as broad beans. Due to its low chemical stability, LD analysis in plant matrices requires an appropriate optimization of the chosen analytical method to obtain reliable results. This work proposes an HPLC-UV method, validated according to EURACHEM guidelines as regards linearity, limits of detection and quantification, precision, accuracy, and matrix effect. The LD extraction was studied by evaluating its aqueous stability over 3 months. The best chromatographic conditions were found by systematically testing several C18 stationary phases and acidic mobile phases. In addition, the assessment of the best storage treatment of Vicia faba L. broad beans able to preserve a high LD content was performed. The best LD determination conditions include sun-drying storage, extraction in HCl 0.1 M, chromatographic separation with a Discovery C18 column, 250 × 4.6 mm, 5 µm particle size, and 99% formic acid 0.2% v/v and 1% methanol as the mobile phase. The optimized method proposed here overcomes the problems linked to LD stability and separation, thus contributing to the improvement of its analytical determination.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Reversed-Phase HPLC Method with UV Detection for the Determination of L-Dopa in Vicia faba L. Broad Beans

et al. 2022

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“…However, when DOPA is in excess, DA shows the wind-up and becomes uncontrollably high. The resulting high DA and DOPA levels can lead to increased and unfavorable oxidative stress by reactions with MAO/ROS leading to cell toxicity and neuropsychiatric disorders [ 30 , 45 , 99 , 100 ].…”

Section: Resultsmentioning

confidence: 99%

DOPA Homeostasis by Dopamine: A Control-Theoretic View

Kleppe

Waheed

Ruoff

2021

IJMS

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Dopamine (DA) is an important signal mediator in the brain as well as in the periphery. The term “dopamine homeostasis” occasionally found in the literature refers to the fact that abnormal DA levels can be associated with a variety of neuropsychiatric disorders. An analysis of the negative feedback inhibition of tyrosine hydroxylase (TH) by DA indicates, with support from the experimental data, that the TH-DA negative feedback loop has developed to exhibit 3,4-dihydroxyphenylalanine (DOPA) homeostasis by using DA as a derepression regulator. DA levels generally decline when DOPA is removed, for example, by increased oxidative stress. Robust DOPA regulation by DA further implies that maximum vesicular DA levels are established, which appear necessary for a reliable translation of neural activity into a corresponding chemical transmitter signal. An uncontrolled continuous rise (windup) in DA occurs when Levodopa treatment exceeds a critical dose. Increased oxidative stress leads to the successive breakdown of DOPA homeostasis and to a corresponding reduction in DA levels. To keep DOPA regulation robust, the vesicular DA loading requires close to zero-order kinetics combined with a sufficiently high compensatory flux provided by TH. The protection of DOPA and DA due to a channeling complex is discussed.

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“…Moreover, it can cause serious side effects, such as dyskinesia [ 6 ]. It accelerates PD progression by inducing neuronal cell death through self-oxidation [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Two Faces of Catechol-O-Methyltransferase Inhibitor on One-Carbon Metabolism in Parkinson’s Disease: A Meta-Analysis

Kim

Jin

et al. 2023

Nutrients

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Levodopa (L−dopa) and catechol−O−methyltransferase (COMT) inhibition are widely used therapeutics in Parkinson’s disease (PD). Despite their therapeutic effects, it was raised that nutrients involved in one−carbon metabolism can be deteriorated by PD therapies. The aim of this meta−analysis was to investigate the impact of L−dopa and COMT inhibitors on levels of homocysteine (Hcy), vitamin B12 and folate in patients with PD. A total of 35 case–control studies from 14 different countries were selected through PubMed, MEDLINE and Google Scholar and were meta−analyzed. In the L−dopa group, the Hcy level was higher compared to the PD without L−dopa group (SMD: 5.11 μmol/L, 95% CI: 3.56 to 6.66). Moreover, vitamin B12 and folate levels in the L−dopa group were lower compared to the healthy control (SMD: −62.67 pg/mL, 95% CI: −86.53 to −38.81; SMD: −0.89 ng/mL, 95% CI: −1.44 to −0.33, respectively). The COMT inhibitor group showed lower levels of Hcy (SMD: −3.78 μmol/L, 95% CI: −5.27 to −2.29) and vitamin B12 (SMD: −51.01 pg/mL, 95% CI: −91.45 to −10.57), but higher folate levels (SMD: 1.78 ng/mL, 95% CI: −0.59 to 4.15) compared to the L−dopa group. COMT inhibitors may ameliorate L−dopa−induced hyper−homocysteine and folate deficiency but exacerbate vitamin B12 deficiency.

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Impairment of neuronal mitochondrial function by l-DOPA in the absence of oxygen-dependent auto-oxidation and oxidative cell damage

Cited by 14 publications

References 82 publications

Development and Validation of a Reversed-Phase HPLC Method with UV Detection for the Determination of L-Dopa in Vicia faba L. Broad Beans

Development and Validation of a Reversed-Phase HPLC Method with UV Detection for the Determination of L-Dopa in Vicia faba L. Broad Beans

DOPA Homeostasis by Dopamine: A Control-Theoretic View

Two Faces of Catechol-O-Methyltransferase Inhibitor on One-Carbon Metabolism in Parkinson’s Disease: A Meta-Analysis

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