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

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.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

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

Mnoge vrste voća i povrća sadržavaju spojeve koji imaju antioksidacijska svojstva, no njihova prerada i skladištenje u prehrambenim pogonima mogu oštetiti te vrijedne sastojke i dovesti do nastanka slobodnih radikala koji zatim uzrokuju oksidacijski stres. Svrha je ovoga rada bila ispitati in vitro antioksidacijski i prooksidacijski učinak pulpe plodova palme Euterpe edulis (juçara) fermentirane s pomoću bakterija Lactobacillus reuteri ili Lactobacillus plantarum, i to prije i nakon sušenja raspršivanjem uz uporabu maltodekstrina, arapske gume ili želatine kao nosača te skladištenja pri 25 °C tijekom 90 dana. Antioksidacijski učinak je procijenjen na osnovi sposobnosti uklanjanja reaktivnih kisikovih spojeva (ROS) tijekom oksidativnog praska neutrofila i slobodnih 2,2-difenil-1-pikril hidrazil (DPPH) radikala, te određivanjem ukupnog udjela fenolnih spojeva. Prooksidacijski učinak je ispitan mjerenjem količine oslobođenih radikala pomoću elektronske paramagnetske rezonancije (EPR). Fermentacija s pomoću obje bakterije povećala je antioksidacijsku aktivnost, dok je sušenje raspršivanjem smanjilo udjel fenolnih spojeva za 65-85 % te sposobnost uklanjanja DPPH radikala, ovisno o upotrijebljenom nosaču. Svi su uzorci inhibirali ROS tijekom oksidativnog praska neutrofila, pri čemu je pulpa fermentirana s pomoću L. reuteri i sušena uz dodatak arapske gume kao nosača imala najveći učinak. Sušenje raspršivanjem nije utjecalo na intenzitet ili vrstu slobodnih radikala detektiranih pomoću metode EPR. Međutim, skladištenjem na sobnoj temperaturi smanjio se antioksidacijski učinak i povećala količina oslobođenih radikala iz fermentirane pulpe.Many fruits and vegetables contain compounds with antioxidant properties, but the processing and storage conditions of the food industry may damage these beneficial compounds and produce free radicals that are associated with oxidative stress. This study aims to evaluate in vitro the antioxidant capacity and prooxidant effects of juçara pulp fermented with Lactobacillus reuteri or Lactobacillus plantarum before and after spray-drying with maltodextrin, gum arabic or gelatin and storage at 25 °C for 90 days. The antioxidant capacity was assessed by measuring the ability to scavenge reactive oxygen species (ROS) in the neutrophil respiratory burst and free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH), and by determining the total phenolic content. The prooxidant effects were analyzed as free radical formation measured by electronic paramagnetic resonance (EPR). Fermentation by both bacteria increased the antioxidant activity, while the spray-drying process decreased the content of phenolic compounds (65-85 %) and the DPPH scavenging ability, depending on the carrier usage. All of the samples inhibited ROS in the neutrophil burst, and the juçara pulp fermented by L. reuteri and dried with gum arabic exhibited the best performance. Spray-drying did not influence the intensity or type of free radicals detected by EPR. However, storage at room temperature decreased the antioxidant capacity and increased free radical formation

Oxidative and nitrosative stress biomarkers in chronic schizophrenia

There is evidence that the acute phase of schizophrenia (SCZ) is accompanied by specific changes in oxidative and nitrosative stress (O&NS) biomarkers. There are, however, no firm data regarding these biomarkers in chronic SCZ. Therefore, this study aimed to delineate O&NS biomarkers in patients with chronic SCZ. 125 outpatients with SCZ and 118 controls were enrolled. The markers included lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP) and paraoxonase 1 (PON-1) activity. Immune-inflammatory markers known to be altered in SCZ were also measured: leptin, IL-6, soluble TNF receptors (sTNF-Rs) and the chemokines CCL-11 and CCL-3. There were no significant associations between chronic SCZ and the O&NS markers (AOPP, NOx, LOOH) and the anti-oxidants PON-1 and TRAP. Leptin, sTNF-R, CCL-3 and CCL-11 were significantly higher in SCZ. There were significant associations between pro-inflammatory and O&NS biomarkers (leptin/CCL-8 and AOPP; IL-6 and NOx; CCL-3 and LOOH; CCL-3/IL-6/NOx and TRAP). In conclusion, there were significant intercorrelations between inflammatory and O&NS pathways, which play a role in the pathophysiology of chronic SCZ. O&NS markers and the enzyme PON-1 are not useful as biomarkers in chronic stable polymedicated SCZ patients

Lowered PON1 activities are strongly associated with depression and bipolar disorder, recurrence of (hypo)mania and depression, increased disability and lowered quality of life

<p><b>Objectives:</b> Mood disorders (MDs) frequently co-exist with cardiovascular disease (CVD) and immune-inflammatory and oxidative stress are important shared pathophysiological pathways. Even though there has been an extensive investigation of the enzyme paraoxonase 1 (PON1) as a biomarker of susceptibility for CVD, there are few reports studying PON1 in MDs. The aim of this study was to determine the association between PON1 activities as well as functional genotypes and MD diagnosis, clinical characteristics and outcomes.</p> <p><b>Methods:</b> PON1 activities and functional genotypes were assayed in 58 bipolar disorder (BD) and 32 major depressed patients (MDD) and compared with 59 controls.</p> <p><b>Results:</b> Our findings show significantly lower PON1 total and CMPAase activities in MDs, which are partly related to the number of previous depressive and manic episodes. Lowered CMPAase activity is associated with a worse outcome of MDs as indicated by lowered quality of life (WHOQoL-BREF scale) and increased disability in the Sheeham scale.</p> <p><b>Conclusions:</b> We hypothesise that lowered PON1 total and CMPAase activities may play a role in the pathophysiology of MDs by lowering antioxidant defences thereby increasing the risk of lipid peroxidation and inflammation; lowered inhibition of quorum-sensing lactones thereby increasing bacterial proliferation; and attenuated homocysteine thiolactone catabolism which may trigger immune-inflammatory response and/or induce neurotoxicity.</p