Comparison of the antioxidant potential of antiparkinsonian drugs in different in vitro models

Abstract

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Furthermore, oxidative stress plays a role in PD, causing or contributing to the neurodegenerative process. Currently PD has only symptomatic treatment and still nothing can be done to stop the degenerative process of the disease. This study aimed to comparatively evaluate the antioxidant capacity of pramipexole, selegeline and amantadine in different in vitro studies and to offer possible explanations on the molecular antioxidant mechanisms of these drugs. In vitro, the antioxidant capacity of the drugs was assessed by the ability of antiparkinsonian drugs to decrease or scavenge ROS in the neutrophil respiratory burst, ability of antiparkinsonian drugs to donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), to scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid (ABTS + ) and evaluation of the ferric reducing antioxidant power (FRAP). This study demonstrated that both pramipexole and selegiline, but not amantadine, have antioxidant effects in vitro by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS + assay and presenting ferric reduction antioxidant power. This chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs beyond their already recognized mechanism of action.Uniterms: Parkinson´s disease. Oxidative stress. Antiparkinsonian drugs/in vitro studies. Antioxidants.A doença de Parkinson (DP) é caracterizada pela degeneração progressiva dos neurônios dopaminérgicos na substância negra pars compacta. Além disso, o estresse oxidativo, presente nesta doença, causa ou contribui para o processo neurodegenerativo. Atualmente, a DP tem apenas tratamento sintomático e ainda nada pode ser feito para interromper o processo degenerativo. Este estudo teve como objetivo avaliar, comparativamente, a capacidade antioxidante do pramipexol, selegilina e amantadina em diferentes testes in vitro e oferecer possíveis explicações sobre os mecanismos moleculares antioxidantes destes fármacos. Avaliou-se a atividade antioxidante dos fármacos através da capacidade em diminuir ou sequestrar espécies reativas de oxigênio no burst respiratório, da capacidade em doar hidrogênio e estabilizar o radical livre 2,2-difenil-1-picril-hidrazil (DPPH•), de remover o radical 2,2'-azino-di-(3-etilbenzotiazolina-6-sulfônico (ABTS + ) e da verificação do poder redutor/antioxidante do ferro (FRAP). Este estudo demonstrou que tanto o pramipexol como a selegilina, mas não a amantadina, possuem efeitos antioxidantes in vitro por eliminar o ânion superóxido no burst respiratório, doar elétrons no método ABTS e apresentar poder redutor sobre o ferro (FRAP). Essa capacidade antioxidante pode estar relacionada com a estrutura química desses medicamentos, sugerindo possíveis mecanismos neuroprotetores destes fármacos além de seus mecanismos de ação já conhecidos. Unitermos: Doença de Parkinson. ...

Influence of Spray-Drying and Room Temperature Storage on the Anti- and Prooxidant Properties of Fermented Juçara Pulp

“…The antioxidant capacity of the juçara pulp may be associated with the presence of phenolic compounds and anthocyanins, whose chemical structures provide reducing power ( 7 , 26 ). The bacterium-specific fermentation differences observed in this study may stem from the characteristics of each species.…”

“…First, fermented juçara pulp was freeze-dried, and then, spray-dried samples were diluted in water to γ =20 μg/mL. Human neutrophils used as a reagent were isolated from whole blood of one healthy young female volunteer, through gradient density centrifugation, and the neutrophil burst was induced by PMA in the presence of fermented juçara pulp samples or phosphate-buffered saline (PBS; control group), according to de Farias et al ( 26 ). Blood used for this technique was taken according to the protocol no.…”

“…Each experimental group had at least 14 replicates and the results were expressed as count per minute (cpm). For the statistical analysis, we used the peak value of each curve, independent of the time when it occurred ( 26 ).…”

Coumarin‐Rasagiline Hybrids as Potent and Selective hMAO‐B Inhibitors, Antioxidants, and Neuroprotective Agents

“…Determination of MAO isoforms in vitro activity . The effects of the coumarin–rasagiline hybrids on h MAO enzymatic activity were evaluated by a fluorimetric method following the experimental protocol previously described by us . Briefly, 50 μL of sodium phosphate buffer (0.05 M, pH 7.4) containing the test drugs (new compounds or reference inhibitors) in different concentrations and adequate amounts of recombinant h MAO‐A or h MAO‐B [adjusted to obtain in our experimental conditions the same reaction velocity ( h MAO‐A: 1.1 μg protein; specific activity: 150 nmol of p ‐tyramine oxidized to p ‐hydroxyphenylacetaldehyde/min/mg protein; h MAO‐B: 7.5 μg protein; specific activity: 22 nmol of p ‐tyramine transformed/min/mg protein)] were incubated for 10 min at 37 °C in a flat‐black bottom 96‐well microtest plate, placed in the dark fluorimeter chamber.…”

Antioxidant Potential of Psychotropic Drugs: From Clinical Evidence to In Vitro and In Vivo Assessment and toward a New Challenge for in Silico Molecular Design

“…Moreover, steric effects limit the availability of the nitrogen electron pair. In a similar fashion, the nitrogen atom in quetiapine does not share its electrons easily, due to the presence of oxygen atoms in the ether and hydroxyl groups [ 53 , 79 ]. These observations are, to some extent, supported by previous experiment by Dietrich-Muszalska et al, in which ziprasidone incubation induced more oxidative stress and lipid peroxidation in samples of plasma from healthy subjects than other antipsychotic drugs [ 71 ].…”